Earthworm Protein Protects Vascular Endothelial Function in Spontaneously Hypertensive Rats via PI3K/Akt/Nrf2 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of earthworm protein on the expression of phosphatidylinositol 3-kinase/protein kinase B/nuclear factor E2-related factor 2 （PI3K/Akt/Nrf2） pathway in the aorta of spontaneously hypertensive rats （SHR） and explore mechanism of earthworm protein in treating hypertensive vascular endothelial dysfunction （VED）. MethodTen 10-week-old Wistar Kyoto （WKY） rats and fifty SHR rats were selected for a week of adaptive feeding. WKY rats were selected as the normal group， and fifty SHR rats were randomized according to body weight into model， valsartan （8×10-3 g·kg-1·d-1）， and high-， medium-， and low-dose （0.2， 0.1， 0.05 g·kg-1·d-1， respectively） earthworm protein groups. The normal and model groups were administrated with equal volume of double distilled water by gavage. During the drug intervention period， the general situations of rats in each group were observed and their blood pressure was monitored at specific time points every other week before and after administration. After 8 weeks of drug intervention， enzyme-linked immunosorbent assay was employed to measure the levels of angiotensin-Ⅱ （Ang-Ⅱ） and endothelin-1 （ET-1） in the serum of rats in each group. The corresponding kits were used to determine the levels of nitric oxide （NO）， malondialdehyde （MDA）， glutathione peroxidase （GPX）， superoxide dismutase （SOD）， and ferrous ion （Fe2+）. Hematoxylin-eosin （HE） staining was employed to observe the changes in the intima of the aorta. Fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to measure the mRNA levels of PI3K， Akt， Nrf2， heme oxygenase-1 （HO-1）， and glutathione peroxidase 4 （GPX4） in the aortic tissue. Western blotting was used to determine the protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 in the thoracic aorta. ResultCompared with the normal group， the model group had decreased body mass， increased irritability， severe endothelial damage， elevated blood pressure and serum levels of Ang-Ⅱ， ET1， MDA， and Fe2+ （P<0.01）， lowered NO level （P<0.01）， and down-regulated mRNA and protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 in the aortic tissue （P<0.01）. Compared with the model group， drug intervention caused no significant change in the body mass， calmed the rats， alleviated the endothelial damage， lowered blood pressure and serum levels of Ang-Ⅱ， ET1， MDA， and Fe2+ （P<0.01）， elevated the NO level （P<0.05）， and up-regulated the mRNA and protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 （P<0.05）. ConclusionThe earthworm protein can exert antihypertensive effects by ameliorating VED in SHR. Specifically， it may regulate the PI3K/Akt/Nrf2 signaling pathway to inhibit oxidative stress and ferroptosis.

El endotelio sano y su disfunción en el riesgo cardiovascular / Healthy Endothelium and its Dysfunction in Cardiovascular Risk

Resumen El endotelio es una monocapa formada por células aplanadas llamadas w, que revisten la parte más interna del corazón, los vasos sanguíneos y los linfáticos. Es considerado un órgano que tiene una función de barrera, pero además se encarga de regular la permeabilidad y tono vascular, hemostasia, inflamación y angiogénesis. Esta revisión se centra sobre todo en las generalidades del endotelio vascular sano y su disfunción. Se analizan los conceptos de activación y disfunción, en donde la activación se considera como un proceso autolimitado, indispensable para la hemostasia y la inflamación. La disfunción endotelial, en cambio, es un proceso patológico, de mayor duración y que se presenta cuando el endotelio ya no puede autorregularse y cambia a un fenotipo proinflamatorio y protrombótico permanente. Esta disfunción es el primer cambio que lleva a la ateroesclerosis y al aumento del riesgo cardiovascular, por esta razón se revisan los principales biomarcadores de disfunción endotelial y riesgo cardiovascular. A medida que se avance en el conocimiento básico del endotelio y su disfunción, será posible diseñar nuevas medidas preventivas o terapéuticas que puedan disminuir dicho riesgo.

Abstract The endothelium is a monolayer of flatten cells named endothelial cells that form the inner layer of the heart, blood, and lymphatic vessels. Its function is not just as a barrier, but it is a regulator of vascular permeability and tone, hemostasis, inflammation, and angiogenesis. This review is about the general aspects of vascular endothelium and endothelial dysfunction that leads to increased vascular risk. Activation and dysfunction are discussed, considering the endothelial activation as a self-limiting process, necessary to promote inflammation and hemostasis. Endothelial dysfunction is a pathological process in which the endothelium loses its ability for self-regulation and acquires a prothrombotic and proinflammation phenotype. Endothelial dysfunction is the initial step for atherosclerosis and increased cardiovascular risk, so the main biomarkers of endothelial dysfunction are reviewed. As basic knowledge about endothelium increases, preventive or therapeutic measures can be designed as treatment or prevention the risk of its dysfunction.

Long-term assessment of systemic microcirculatory function and plasma cytokines after coronavirus disease 2019 (COVID-19)

Abstract Systemic microvascular dysfunction has been shown to be present in COVID-19, and serum cytokines are known to be involved in the regulation of vascular function. We sought to evaluate systemic microvascular endothelial function, with laser doppler perfusion monitoring (LDPM), and plasma levels of cytokines after acute COVID-19. Individuals admitted to a Cardiology hospital with acute COVID-19 and followed for 12-15 months after recovery underwent noninvasive evaluation of systemic endothelium-dependent microvascular reactivity by cutaneous LDPM with local thermal hyperemia (LTH). A multiplex biometric immunoassay panel was used to assess 48 serum cytokines and chemokines. Twenty patients and 14 control volunteers were enrolled. The areas under the curves of vasodilation induced by LTH were significantly increased after recovery (P=0.009) and were not different from values obtained in healthy volunteers (P= 0.85). The peak microvascular flow during LTH did also significantly increase (P= 0.02), and was not different form values obtained in healthy volunteers (P= 0.55). Several cytokines displayed significantly reduced serum concentrations after recovery from COVID-19. In conclusion, endothelium-dependent systemic microvascular reactivity improved after recovery from COVID-19 in patients with cardiovascular diseases, in parallel with a reduction in the levels of several serum cytokines and chemokines involved in the regulation of vascular function and inflammation.

Endothelial Dysfunction and Diabetes: An Ayurvedic Concept

Diabetes mellitus is associated with an increased risk of cardiovascular disease, even in the presence of intensive glycaemic control. Both diabetes and insulin resistance bring about a amalgam of endothelial dysfunction and it will abate the anti-atherogenic role of the vascular endothelium. In patients with type 2 diabetes both insulin resistance and endothelial dysfunction appear to lead up to the development of undisguised hyperglycaemia. Hence, in patients with diabetes, endothelial dysfunction may be a censorious early intention for preventing atherosclerosis and cardiovascular disease. For the assessment endothelium- dependent vasodilatation Coronary and peripheral circulations are used. In Ayurveda, endothelial dysfunction can be correlated to Rakthavaha srotho dushti. There are several aetiological factors similar in both Prameha and Rakta dushti. The factors which got vitiated (Dooshya) in Prameha are Mamsa, Meda, Rasa, Rakta, Shukra, Lasika, Vasa, Majja & Oja. Amongst all Meda & Mamsa are main vitiated factors (Dooshya) while Rakta is one of the Dooshya initially. During nourishment, Rakta is nourished prior to Meda & Mamsa. Further it nourishes Meda dhatu too. Endothelial dysfunction is reversible in early stages so that many rasayana drugs mentioned in the Ayurveda can be used here. In the present review briefly outlines some basic concepts of endothelial structure and function, and its dysfunction, relation with diabetes and its Ayurvedic concepts and management.

Trimethylamine oxide induces pyroptosis of vascular endothelial cells through ALDH2/ROS/NLRP3/GSDMD pathway / 中南大学学报(医学版)

Objective: Trimethylamine oxide (TMAO) is a metabolite of intestinal flora and is known to promote the progression of atherosclerotic plaques. However, how TMAO works, including its effect on vascular endothelial cells, is not fully understood. This study aims to explore the biological role of TMAO in human umbilical vein endothelial cells (HUVECs) and the underlying mechanism. Methods: Cell pyroptosis and the loss of plasma membrane integrity were induced under TMAO stimulation in HUVECs. The plasma membrane integrity of the cells was measured by Hoechst 33342/propidium iodide (PI) staining and lactate dehydrogenase leakage assay, and the changes in cell morphology were observed by atomic force microscope. The expression of proteins related to pyroptosis was determined by Western blotting or immunofluorescence. Mitochondrial acetaldehyde dehydrogenase 2 (ALDH2) activity in HUVECs was measured by the ALDH2 activity assay kit, and the level of reactive oxygen species (ROS) was detected by fluorescent probe DCFH-DA. Results: TMAO induced pyroptotic cell death, manifesting by the presence of propidium iodide-positive cells, the leakage of lactate dehydrogenase, the production of N-terminal gasdermin D (GSDMD-N), and the formation of plasma membrane pores. Moreover, TMAO induced elevated expression of inflammasome components, nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3),apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), and caspase-1 in cells. TMAO significantly inhibited ALDH2 activity and increased intracellular ROS production. However, the activation of ALDH2 by pharmacological manipulation attenuated TMAO-induced inflammasome activation and GSDMD-N production.Conclusion: TMAO induces pyroptosis of vascular endothelial cells through the ALDH2/ROS/NLRP3/GSDMD signaling pathway, which may be a potential therapeutic target for improving the treatment of atherosclerosis.

Resveratrol attenuates chronic pulmonary embolism-related endothelial cell injury by modulating oxidative stress, inflammation, and autophagy

Abstract Objectives: Due to Pulmonary Artery Endothelial Cell (PAEC) dysfunction, Pulmonary Hypertension (PH) persists even after the Pulmonary Embolism (PE) has been relieved. However, the mechanism behind this remains unclear. Method: Here, the authors incubated Human PAECs (HPAECs) with thrombin to simulate the process of arterial thrombosis. Results: CCK8 results showed a decrease in the viability of HPAECs after thrombin incubation. In addition, the expression of Tissue Factor (TF), Monocyte Chemoattractant Protein 1 (MCP-1), VCAM-1, ICAM-1, cleaved cas-pase 3, cleaved caspase 9, and Bax protein were all increased after thrombin incubation, while Bcl-2 was decreased. The effects of 3-MA treatment further suggested that autophagy might mediate the partial protective effects of Resveratrol on HPAECs. To observe the effects of Resveratrol in vivo, the authors established a Chronic Thromboembolic Pulmonary Hypertension (CTEPH) model by repeatedly injecting autologous blood clots into a rat's left jugular vein. The results exhibited that Mean Pulmonary Arterial Pressure (mPAP) and vessel Wall Area/ Total Area (WA/TA) ratio were both decreased after Resveratrol treatment. Moreover, Resveratrol could reduce the concentration and activity of TF, vWF, P-selectin, and promote these Superoxide Dismutase (SOD) in plasma. Western blot analysis of inflammation, platelet activation, autophagy, and apoptosis-associated proteins in pulmonary artery tissue validated the results in PHAECs. Conclusions: These findings suggested that reduced autophagy, increased oxidative stress, increased platelet activation, and increased inflammation were involved in CTEPH-induced HPAEC dysfunction and the development of PH, while Resveratrol could improve PAEC dysfunction and PH.

Intravenous whole blood transfusion results in faster recovery of vascular integrity and increased survival in experimental cerebral malaria

BACKGROUND Cerebral malaria is a lethal complication of Plasmodium falciparum infections in need of better therapies. Previous work in murine experimental cerebral malaria (ECM) indicated that the combination of artemether plus intraperitoneal whole blood improved vascular integrity and increased survival compared to artemether alone. However, the effects of blood or plasma transfusion administered via the intravenous route have not previously been evaluated in ECM. OBJECTIVES To evaluate the effects of intravenous whole blood compared to intravenous plasma on hematological parameters, vascular integrity, and survival in artemether-treated ECM. METHODS Mice with late-stage ECM received artemether alone or in combination with whole blood or plasma administered via the jugular vein. The outcome measures were hematocrit and platelets; plasma angiopoietin 1, angiopoietin 2, and haptoglobin; blood-brain barrier permeability; and survival. FINDINGS Survival increased from 54% with artemether alone to 90% with the combination of artemether and intravenous whole blood. Intravenous plasma lowered survival to 18%. Intravenous transfusion provided fast and pronounced recoveries of hematocrit, platelets, angiopoietins levels and blood brain barrier integrity. MAIN CONCLUSIONS The outcome of artemether-treated ECM was improved by intravenous whole blood but worsened by intravenous plasma. Compared to prior studies of transfusion via the intraperitoneal route, intravenous administration was more efficacious.

Alphacalcidol Supplementation Improves AcetylcholineMediated Relaxation in Aorta of Diabetic Rats on Vitamin D-Deficient Diet

@#Introduction: Vitamin D deficiency has been implicated as one of the factors involved in endothelial dysfunction associated with diabetes. This study aimed to evaluate the effects of active vitamin D (alphacalcidol) supplementation on aortic endothelial function in diabetic rats receiving vitamin D-deficient diet. Methods: Streptozotocin-induced diabetic rats were fed with standard diet (D) or vitamin D-deficient diet (DD and DDS) for 10 weeks. Group DDS was then supplemented with 0.2 μg/kg alphacalcidol at the last four weeks of the study duration. Non-diabetic rats were fed with standard diet (N) or vitamin-D deficient diet (ND). At the end of the experiment, the rats were sacrificed, and their aortic rings were harvested for endothelial functional study. Results: Acetylcholine-induced relaxation in aorta of diabetic rats (D and DD) were significantly lower compared to non-diabetic rats (N). In the presence of endothelial nitric oxide synthase blocker (L-NAME), maximal relaxation induced by acetylcholine in aorta of D and DD groups were significantly higher compared to N, ND and DDS groups, indicating involvement of non-nitric oxide (NO) relaxation pathways in diabetes. Four weeks supplementation with alphacalcidol in DDS group significantly improved acetylcholine-induced relaxation and reduced the reliance on non-NO relaxation pathways. Conclusion: The present study suggests that impairment of acetylcholine-induced relaxation in aorta of diabetes and diabetes with vitamin D-deficient diet was largely due to a decrease in NO related pathways, and this was compensated by non-NO pathways. Supplementation with alphacalcidol alleviated endothelial impairment in aorta of diabetic rats with vitamin D-deficient diet.

Influence of Endothelial Dysfunction on Diabetic Macroangiopathy： A Perspective from Theory of "Restraining Excessiveness to Acquire Harmony" / 中国实验方剂学杂志

The normal function of vascular endothelial cells is an important foundation for maintaining vascular permeability， restricting inflammatory activities of the vascular wall， and balancing the coagulation and fibrinolytic system. Endothelial dysfunction caused by persistent damage from pathological factors is considered as an early and prominent event of diabetic macroangiopathy. In traditional Chinese medicine， the classical theory of "restraining excessiveness to acquire harmony" was originally a condensed generalization of the rule of generation， restriction， replacement and evolution in the natural world， revealing the internal regulation mechanism of the stable operation of things. Then it gradually evolved into an important rule to explain the physiological phenomena and pathological mechanism of human body and guide the treatment. Corresponding to the nature， the body homeostasis also requires to achieve a state of strong viscera function and inexhaustible Qi and blood generation under the rule of restriction and generation. The pathogenesis of diabetic macroangiopathy is the process of "the predominant one failing to restrict and the hyperactive one becoming harmful". The loss of restriction and generation of the five organs leads to powerless Qi transformation and， as a result， the Qi， blood and body fluid cannot be dispersed. Therefore， the Qi， blood and body fluid turn into phlegm and blood stasis， such as glucose and lipid metabolism disorder， oxidative stress， inflammatory response and high blood viscosity， and finally block the veins. Excessive phlegm and blood stasis cannot be resolved， instead they become harmful and invade the blood vessel， causing endothelial dysfunction and further resulting in diabetic macroangiopathy. Under the guidance of the theory of "restraining excessiveness to acquire harmony"， the method of "harmonizing viscera， eliminating pathogen and removing turbidity" can effectively regulate the function of vascular endothelial cells， thus playing a positive role in preventing and treating diabetic macroangiopathy. The mechanism may be related to reducing oxidative stress， inhibiting inflammation， limiting vascular smooth muscle proliferation， and reducing platelet adhesion.

Influence of electroacupuncture on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase signaling pathway in spontaneously hypertensive rats / 中西医结合学报

OBJECTIVE@#To investigate the influence of electroacupuncture (EA) on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase (PI3K/Akt/eNOS) signaling pathway in spontaneously hypertensive rats (SHRs).@*METHODS@#Eight Wistar-Kyoto rats were used as the healthy blood pressure (BP) control (normal group), and 32 SHRs were randomized into model group, EA group, EA plus ghrelin group (EA + G group), and EA plus PF04628935 group (a potent ghrelin receptor blocker; EA + P group) using a random number table. Rats in the normal group and model group did not receive treatment, but were immobilized for 20 min per day, 5 times a week, for 4 continuous weeks. SHRs in the EA group, EA + G group and EA + P group were immobilized and given EA treatment in 20 min sessions, 5 times per week, for 4 weeks. Additionally, 1 h before EA, SHRs in the EA + G group and EA + P group were intraperitoneally injected with ghrelin or PF04628935, respectively, for 4 weeks. The tail-cuff method was used to measure BP. After the 4-week intervention, the rats were sacrificed by cervical dislocation, and pathological morphology of the abdominal aorta was observed using hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of ghrelin, nitric oxide (NO), endothelin-1 (ET-1) and thromboxane A2 (TXA2) in the serum. Isolated thoracic aortic ring experiment was performed to evaluate vasorelaxation. Western blot was used to measure the expression of PI3K, Akt, phosphorylated Akt (p-Akt) and eNOS proteins in the abdominal aorta. Further, quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to measure the relative levels of mRNA expression for PI3K, Akt and eNOS in the abdominal aorta.@*RESULTS@#EA significantly reduced the systolic BP (SBP) and diastolic BP (DBP) (P < 0.05). HE staining showed that EA improved the morphology of the vascular endothelium to some extent. Results of ELISA indicated that higher concentrations of ghrelin and NO, and lower concentrations of ET-1 and TXA2 were presented in the EA group (P < 0.05). The isolated thoracic aortic ring experiment demonstrated that the vasodilation capacity of the thoracic aorta increased in the EA group. Results of Western blot and qRT-PCR showed that EA increased the abundance of PI3K, p-Akt/Akt and eNOS proteins, as well as expression levels of PI3K, Akt and eNOS mRNAs (P < 0.05). In the EA + G group, SBP and DBP decreased (P < 0.05), ghrelin concentrations increased (P < 0.05), and the concentrations of ET-1 and TXA2 decreased (P < 0.05), relative to the EA group. In addition, the levels of PI3K and eNOS proteins, the p-Akt/Akt ratio, and the expression of PI3K, Akt and eNOS mRNAs increased significantly in the EA + G group (P < 0.05), while PF04628935 reversed these effects.@*CONCLUSION@#EA effectively reduced BP and protected the vascular endothelium, and these effects may be linked to promoting the release of ghrelin and activation of the PI3K/Akt/eNOS signaling pathway.

Intensidad del síndrome vasomotor y su relación con la función endotelial en mujeres de edad mediana / Intensity of the vasomotor syndrome and its relation with endothelial function in middle age women

Introducción: El síndrome vasomotor constituye la manifestación clínica más frecuente de la transición menopaúsica y a menudo se asocia con cambios en la función endotelial. Objetivo: Determinar la relación entre la intensidad del síndrome vasomotor y la función endotelial en mujeres de edad mediana aparentemente sanas. Método: Estudio descriptivo transversal, en 133 mujeres de 40-59 años sin factores de riesgo cardiovascular. Se excluyeron aquellas mujeres con menopausia quirúrgica, uso previo de terapia hormonal de reemplazo seis meses antes. Se evaluó la función endotelial mediante la prueba de dilatación mediada por el flujo de la arteria braquial, y la intensidad del síndrome vasomotor mediante la escala de Pérez Piñeiro. Las mujeres fueron distribuidas en dos subgrupos: uno con disfunción endotelial y el otro con función endotelial normal. Para identificar la asociación entre variables se utilizó la prueba Kruskal-Wallis y la prueba Chi Cuadrado para evaluar la significación estadística, considerándose significativos los valores de p < 0,05. Resultados: El 63 por ciento de las mujeres presentaron síndrome vasomotor, 29 de intensidad leve, 31 moderado y muy molesto 33 mujeres. Del total de mujeres, 51 tuvieron disfunción endotelial, para un 38,3 por ciento, mostrando un promedio de dilatación dependiente del endotelio de 1,81±1,57 cm. No se encontró asociación significativa entre la intensidad del síndrome vasomotor y la función endotelial p = 0,139. Conclusiones: La intensidad del síndrome vasomotor no se relacionó con la disfunción endotelial en mujeres de edad mediana. Se necesita ampliar la muestra y realizar estudios prospectivos para identificar el daño vascular en ese grupo de mujeres(AU)

Introduction: The vasomotor syndrome is the most frequent clinical manifestation of the menopausal transition and it is often associated with changes in the endothelial function. Objective: Determine the relation among the intensity of the vasomotor syndrome and the endothelial function in apparently healthy middle age women. Methods: Descriptive cross-sectional study in 113 women of 40-59 years without cardiovascular risk factors. There were excluded women with surgical menopause, and use of replacement hormonal therapy six months before. It was assessed the endothelial function through the dilation test and the flow of the brachial artery, and the intensity of the vasomotor syndrome through the scale of Pérez. The women were organized in two groups: one group of women with endothelial dysfunction and the other of women with normal endothelial function. It was used the Kruskal-Wallis test to identify the association among variables and the chi-Square test to assess the statistical significance considering important the values of p < 0.05. Results: 63 percent of the women presented vasomotor syndrome, 29 of them of slight intensity, 31 moderate and 33 women had a very uncomfortable one. Of the total, 51 women presented endothelial dysfunction representing a 38.3 percent and showing an average of dilation dependant of endothelium of 1.81±1.57 cm. There was not found significant association among the intensity of the vasomotor syndrome and the endothelial function p = 0.139. Conclusions: The intensity of the vasomotor syndrome was not related with the endothelial dysfunction in middle age women. It is needed to expand the sample and to implement prospective studies in order to identify the vascular damage in that group of women(AU)

Manifestaciones pulmonares y sistémicas de la hipertensión arterial pulmonar: Un enfoque panvascular

La hipertensión arterial pulmonar (HAP) es una grave enfermedad cuyo resultado final de la interacción entre el tono vascular y la alteración progresiva de la remodelación de las arterias pulmonares provoca insuficiencia cardíaca derecha y muerte. El remodelado vascular pulmonar es la alteración estructural clave en la hipertensión pulmonar. Este proceso implica cambios en la íntima, media, adventicia y espacio perivascular, a menudo con la interacción de células inflamatorias. Los mecanismos fisiopatológicos de la HAP abarcan una serie de modificaciones vasculares que producen un aumento de la resistencia vascular pulmonar. Las modificaciones vasculares que se producen en la HAP incluyen: la vasoconstricción, la proliferación del músculo liso, la inflamación, la apoptosis endotelial, la proliferación endotelial resistente a la apoptosis, la fibrosis, la trombosis in-situ, y finalmente, las lesiones plexiformes. Hasta hace poco, la HAP se consideraba una enfermedad restringida a la circulación pulmonar. Sin embargo, existe una creciente evidencia de que los pacientes con HAP también exhiben disfunción vascular sistémica, como lo demuestra la alteración de la dilatación mediada por el flujo de la arteria braquial, el flujo sanguíneo cerebral anormal, la miopatía esquelética y la enfermedad renal intrínseca. Los datos recientes apoyan un vínculo con los eventos genéticos y moleculares detrás de la patogénesis de la HAP. Esta revisión sirve de introducción a los principales hallazgos sistémicos en la HAP y la evidencia que apoya un vínculo común con la fisiopatología de la HAP. Sobre la base de la evidencia disponible, proponemos un paradigma en el que las anomalías metabólicas, la lesión genética y la disfunción vascular sistémica contribuyen a las manifestaciones sistémicas de la HAP. Este concepto no sólo abre interesantes posibilidades de investigación, sino que también anima a considerar las manifestaciones extrapulmonares en el tratamiento de los pacientes con HAP, pues la disfunción vascular sistémica contribuiría a las manifestaciones sistémicas de la HAP.

Pulmonary arterial hypertension (PAH) is a serious disease whose end result of the interaction between vascular tone and the progressive alteration of the remodeling of the pulmonary arteries causes right heart failure and death. Pulmonary vascular remodeling is the key structural alteration in pulmonary hypertension. This process involves changes in the intima, media, adventitia, and perivascular space, often with the interaction of inflammatory cells. The pathophysiological mechanisms of PAH include a series of vascular modifications that produce an increase in pulmonary vascular resistance. Vascular modifications that occur in PAH include: vasoconstriction, proliferation of smooth muscle, inflammation, Endothelial apoptosis, apoptosis-resistant endothelial proliferation, fibrosis, in-situ thrombosis, and finally, plexiform lesions. Until recently, PAH was considered a disease restricted to the pulmonary circulation. However, there is growing evidence that patients with PAH also exhibit systemic vascular dysfunction, as evidenced by impaired brachial artery flow-mediated dilation, abnormal cerebral blood flow, skeletal myopathy, and intrinsic kidney disease. Recent data support a link to the genetic and molecular events behind the pathogenesis of PAH. This review serves as an introduction to the main systemic findings in PAH and the evidence supporting a common link with the pathophysiology of PAH. Based on the available evidence, we propose a paradigm in which metabolic abnormalities, genetic injury, and systemic vascular dysfunction contribute to the systemic manifestations of PAH. This concept not only opens up interesting research possibilities, but also encourages consideration of extrapulmonary manifestations in the treatment of patients with PAH, since systemic vascular dysfunction would contribute to the systemic manifestations of PAH.

A hipertensão arterial pulmonar (HAP) é uma doença grave cujo resultado final da interação entre o tônus vascular e a alteração progressiva da remodelação das artérias pulmonares causa insuficiência cardíaca direita e morte. A remodelação vascular pulmonar é a principal alteração estrutural na hipertensão pulmonar. Esse processo envolve mudanças na íntima, média, adventícia e espaço perivascular, muitas vezes com a interação de células inflamatórias. Os mecanismos fisiopatológicos da HAP incluem uma série de modificações vasculares que produzem um aumento na resistência vascular pulmonar. As modificações vasculares que ocorrem na HAP incluem: vasoconstrição, proliferação do músculo liso, inflamação, apoptose endotelial, proliferação endotelial resistente à apoptose, fibrose, trombose in situ e, finalmente, lesões plexiformes. Até recentemente, a HAP era considerada uma doença restrita à circulação pulmonar. No entanto, há evidências crescentes de que os pacientes com HAP também apresentam disfunção vascular sistêmica, conforme evidenciado pela dilatação prejudicada mediada pelo fluxo da artéria braquial, fluxo sanguíneo cerebral anormal, miopatia esquelética e doença renal intrínseca. Dados recentes suportam uma ligação com os eventos genéticos e moleculares por trás da patogênese da HAP. Esta revisão serve como uma introdução aos principais achados sistêmicos em HAP e as evidências que apoiam uma ligação comum com a fisiopatologia da HAP. Com base nas evidências disponíveis, propomos um paradigma em que anormalidades metabólicas, lesão genética e disfunção vascular sistêmica contribuem para as manifestações sistêmicas da HAP. Esse conceito não apenas abre possibilidades interessantes de pesquisa, mas também incentiva a consideração das manifestações extrapulmonares no tratamento de pacientes com HAP, uma vez que a disfunção vascular sistêmica contribuiria para as manifestações sistêmicas da HAP.

Sang-Yod rice bran hydrolysates alleviate hypertension, endothelial dysfunction, vascular remodeling, and oxidative stress in nitric oxide deficient hypertensive rats

Objective: To evaluate the potential therapeutic effect of Sang-Yod rice bran hydrolysates (SRH) and in combination with lisinopril against hypertension, endothelial dysfunction, vascular remodeling, and oxidative stress in rats with nitric oxide deficiency-induced hypertension. Methods: Hypertension was induced in male Sprague-Dawley rats by administration of a nitric oxide synthase inhibitor, Nω- nitro-L-arginine methyl ester (L-NAME) in drinking water for 6 weeks. Hypertensive rats were administered daily with SRH (500 mg/kg/day), lisinopril (1 mg/kg/day), or the combination of SRH and lisinopril by gastric lavage for the last 3 weeks of L-NAME treatment. Hemodynamic status, vascular reactivity to vasoactive agents, and vascular remodeling were assessed. Blood and aortic tissues were collected for measurements of oxidative stress markers, plasma angiotensin-converting enzyme (ACE) activity, plasma angiotensin II, and protein expression. Results: L-NAME induced remarkable hypertension and severe oxidative stress, and altered contents of smooth muscle cells, elastin, and collagen of the aortic wall. SRH or lisinopril alone reduced blood pressure, restored endothelial function, decreased plasma ACEs and angiotensin II levels, alleviated oxidant markers and glutathione redox status, and restored the vascular structure. The effects were associated with increased expression of endothelial nitric oxide synthase and decreased expression of gp91phox and AT1R expression. The combination of SRH and lisinopril was more effective than monotherapy. Conclusions: SRH alone or in combination with lisinopril exert an antihypertensive effect and improve endothelial function and vascular remodeling through reducing oxidative stress and suppressing elevated renin-angiotensin system.

Parámetros de laboratorio de importancia en el manejo de pacientes con COVID-19 / Laboratory parameters of importance in the management of COVID-19 patients

Resumen El coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2) detona el padecimiento la enfermedad por coronavirus 2019 (COVID-19), poniendo en riesgo de muerte a la población vulnerable. El laboratorio clínico enfrenta un reto para el diagnóstico, seguimiento, pronóstico y evaluación de los tratamientos, que se ofrecen a los enfermos de COVID-19. Nuestro objetivo es mostrar al lector un resumen de los principales cambios en los parámetros que se estudian en los laboratorios clínicos. Material y métodos: Se hizo una búsqueda bibliográfica cruzando los términos COVID-19 y laboratorio clínico. Se analizaron las publicaciones relevantes por los miembros del Comité de Trombosis y Hemostasia-AMEH A.C. y se plasmaron las pruebas que a criterio de los participantes destacan por la relación entre la información que proporcionan respecto al seguimiento, pronóstico y evaluación al tratamiento. Resultados: Se recomienda solicitar una citometría hemática (recuento de células blancas, relación neutrófilo:linfocito), química sanguínea (transaminasas, bilirrubinas, albúmina, urea, creatinina, glucosa, lactato deshidrogenasa), pruebas de coagulación (tiempo de protrombina, tiempo de tromboplastina parcial activado, fibrinógeno y dímeros D) y pruebas especiales (proteína C reactiva, ferritina, procalcitonina, troponina).

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggers the coronavirus disease 2019 (COVID-19), putting the vulnerable population at risk of death. The clinical laboratory faces a challenge for the diagnosis, monitoring, prognosis and evaluation of therapy with low molecular weight heparin. Our objective in this article is to offer a brief discuss of the main changes in the clinical parameters, studied on behalf of COVID-19 patients by a clinical laboratory. Material and methods: A bibliographic search was made crossing the terms COVID-19 and clinical laboratory. Relevant publications were analyzed by the members of the Committee for Thrombosis and Hemostasis-AMEH A.C. The relevant articles were discussed, and the clinical tests discussed in the article are those, that meet the criteria of providing information referring to the follow-up, prognosis and evaluation of treatment against the lower cost. Results: It is recommended to request a blood count (white cell count, neutrophyl/ lymphocytes ratio), clinical chemistry (transaminases, bilirubin, albumin, urea, creatinine, glucose, lactate dehydrogenase), coagulation tests (prothrombin time, activated partial thromboplastin time, fibrinogen, DD dimers) and special tests (C-reactive protein, ferritin, procalcitonin, troponins).

The effect of weight loss on endothelial function and cerebrovascular risk factors in obese and overweight people / 中华健康管理学杂志

Objective:To explore the effect of weight loss on endothelial function and cerebrovascular risk factors in obese and overweight people.Methods:A total of 127 obese or overweight subjects received 6-month body weight management. Subjects who lost 3 kg or more than 5% of their body weight prior to the 6-month intervention were defined as achievement group. Endothelial function (FMD) and other cerebrovascular risk factors were measured before and after intensified lifestyle management.Results:The achievement group comprised 57 (44.9%) cases and the non-achievement group 70 (55.1%) cases. After 6-month intervention, FMD (6.98±2.88% vs 7.90±2.96%, P<0.05) and HDL-C increased in the achievement group. Significant decreases were observed in the achievement group in BMI, SBP, DBP, FPG, TC, LDL-C, TG and uric acid. However, only DBP and FPG decreased in the non-achievement group. Conclusion:Weight loss can reverse endothelial dysfunction and metabolic dysfunction. Decrease of body fat ratio contributes to the improvement of endothelial function.

Sang-Yod rice bran hydrolysates alleviate hypertension, endothelial dysfunction, vascular remodeling, and oxidative stress in nitric oxide deficient hypertensive rats

Objective: To evaluate the potential therapeutic effect of Sang-Yod rice bran hydrolysates (SRH) and in combination with lisinopril against hypertension, endothelial dysfunction, vascular remodeling, and oxidative stress in rats with nitric oxide deficiency-induced hypertension. Methods: Hypertension was induced in male Sprague-Dawley rats by administration of a nitric oxide synthase inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME) in drinking water for 6 weeks. Hypertensive rats were administered daily with SRH (500 mg/kg/day), lisinopril (1 mg/kg/day), or the combination of SRH and lisinopril by gastric lavage for the last 3 weeks of L-NAME treatment. Hemodynamic status, vascular reactivity to vasoactive agents, and vascular remodeling were assessed. Blood and aortic tissues were collected for measurements of oxidative stress markers, plasma angiotensin-converting enzyme (ACE) activity, plasma angiotensinⅡ, and protein expression. Results: L-NAME induced remarkable hypertension and severe oxidative stress, and altered contents of smooth muscle cells, elastin, and collagen of the aortic wall. SRH or lisinopril alone reduced blood pressure, restored endothelial function, decreased plasma ACEs and angiotensinⅡlevels, alleviated oxidant markers and glutathione redox status, and restored the vascular structure. The effects were associated with increased expression of endothelial nitric oxide synthase and decreased expression of gp91phox and AT1R expression. The combination of SRH and lisinopril was more effective than monotherapy. Conclusions: SRH alone or in combination with lisinopril exert an antihypertensive effect and improve endothelial function and vascular remodeling through reducing oxidative stress and suppressing elevated renin-angiotensin system.

Endothelial dysfunction in COVID-19 calls for immediate attention: the emerging roles of the endothelium in inflammation caused by SARS-CoV-2 / 医学前沿

The COVID-19 pandemic has caused numerous deaths around the world. A growing body of evidence points to the important role of overwhelming inflammatory responses in the pathogenesis of COVID-19 and the effectiveness of anti-inflammation therapy against COVID-19 is emerging. In addition to affecting the lungs, COVID-19 can be a severe systemic inflammatory disease that is related to endothelial dysfunction. We are calling for closer attention to endothelial dysfunction in COVID-19 not only for fully revealing the pathogenic mechanism of COVID-19 but also for properly adjusting the strategy of clinical intervention.

Research Progress of Adipokine and Kidney Disease / 中国医学科学院学报

Adipokines,the bioactive polypeptides secreted by adipose tissue,are related to the occurrence and development of obesity,metabolic syndrome,renal insufficiency,cardiovascular disease,diabetes mellitus and other diseases.They may be the disease intervention targets and a breakthrough in the study of disease pathogenesis.In this paper,we summarize the latest research progress of the adipokines omentin,chemerin and nesfatin.

Uric acid as a predictor of endothelial dysfunction in patients with metabolic syndrome

ABSTRACT Objective: We conducted a study to examine the association of endothelial dysfunction and oxidative stress with uric acid levels in patients of metabolic syndrome. Subjects and methods: One hundred and two patients of Metabolic Syndrome (International Diabetes Federation definition) were included in the study. Anthropometric measurements, serum uric acid levels, fasting blood sugar levels and lipid levels, as well as malondialdehyde and reactive nitrogen intermediates were measured after an 8-hour fasting period. Flow mediated vasodilation (FMD) of the brachial artery was measured and endothelial dysfunction was defined as an increase in diameter < 10% post compression. Results: A total of 102 patients were included in the study. Mean uric acid level was 5.49 ± 1.61 mg%. A total of 59 patients in the study had endothelial dysfunction, defined by an abnormal FMD. Patients with an abnormal FMD had higher levels of serum uric acid which was statistically significant (p value = 0.010). Serum RNI and MDA levels were negatively correlated with uric acid, but did not reach statistical significance. Patients with an abnormal FMD had a lower RNI level, but this did not reach statistical significance. Serum MDA levels were significantly higher in patients with an abnormal FMD (p value = 0.038). Conclusions: Uric acid was significantly associated with endothelial dysfunction in patients with metabolic syndrome in our study. It was inversely correlated with serum RNI and MDA levels, but this did not reach statistical significance.

Relación entre periodontitis y disfunción eréctil: ¿realidad o mito? / Relationship between periodontitis and erectile dysfunction: reality or myth?

Introducción: Se realiza una revisión bibliográfica con base en artículos científicos con la finalidad de exponer la posible relación entre periodontitis (PD) y disfunción eréctil (DE), así como las variables contundentes que se encuentran implicadas. Material y métodos: Como estrategia de búsqueda primaria se emplea una combinación de vocabulario controlado (erectile dysfunction and periodontal disease) y términos de texto libre basado en la estrategia de búsqueda en MEDLINE a través de PubMed. Como estrategia de búsqueda secundaria se revisaron las referencias bibliográficas contenidas en los artículos seleccionados. Resultados: Diez estudios de casos y controles encontraron asociaciones positivas significativas entre estas dos condiciones. Conclusión: La evidencia de la literatura indica un vínculo positivo entre la PD y la DE (AU)

Introduction: A bibliographic review was carried out in scientific articles in order to expose the possible relationship between periodontitis (PD) and erectile dysfunction (ED), as well as the overwhelming variables that are involved. Material and methods: A combination of controlled vocabulary (erectile dysfunction and periodontal disease) and free text terms based on the MEDLINE search strategy through PubMed was used as the primary search strategy. As a secondary search strategy, the bibliographic references contained in the selected articles were reviewed. Results: Ten case-control studies found significant positive associations between these two conditions. Conclusion: The evidence in the literature indicates a positive link between PD and ED (AU)