lncR-GAS5 upregulates the splicing factor SRSF10 to impair endothelial autophagy, leading to atherogenesis / 医学前沿

Long noncoding RNAs (lncRNAs) play a critical role in the regulation of atherosclerosis. Here, we investigated the role of the lncRNA growth arrest-specific 5 (lncR-GAS5) in atherogenesis. We found that the enforced expression of lncR-GAS5 contributed to the development of atherosclerosis, which presented as increased plaque size and reduced collagen content. Moreover, impaired autophagy was observed, as shown by a decreased LC3II/LC3I protein ratio and an elevated P62 level in lncR-GAS5-overexpressing human aortic endothelial cells. By contrast, lncR-GAS5 knockdown promoted autophagy. Moreover, serine/arginine-rich splicing factor 10 (SRSF10) knockdown increased the LC3II/LC3I ratio and decreased the P62 level, thus enhancing the formation of autophagic vacuoles, autolysosomes, and autophagosomes. Mechanistically, lncR-GAS5 regulated the downstream splicing factor SRSF10 to impair autophagy in the endothelium, which was reversed by the knockdown of SRSF10. Further results revealed that overexpression of the lncR-GAS5-targeted gene miR-193-5p promoted autophagy and autophagic vacuole accumulation by repressing its direct target gene, SRSF10. Notably, miR-193-5p overexpression decreased plaque size and increased collagen content. Altogether, these findings demonstrate that lncR-GAS5 partially contributes to atherogenesis and plaque instability by impairing endothelial autophagy. In conclusion, lncR-GAS5 overexpression arrested endothelial autophagy through the miR-193-5p/SRSF10 signaling pathway. Thus, miR-193-5p/SRSF10 may serve as a novel treatment target for atherosclerosis.

Lipoproteínas ricas en triglicéridos y riesgo cardiovascular residual / Triglyceride rich lipoproteins and residual cardiovascular risk / Lipoproteínas ricas em triglicerídeos e risco cardiovascular residual / Reconocimiento a la trayectoria del Prof. Dr. Juan Miguel Castagnino†

Resumen Una vasta evidencia científica de resultados de ensayos clínicos, preclínicos, epidemiológicos y genéticos, mostraron una asociación causal entre el aumento de triglicéridos (TG), lipoproteínas ricas en TG (LRT) y sus remanentes para la enfermedad cardiovascular aterosclerótica (ECA). La acumulación de LRT circulantes puede explicar, en parte, el riesgo cardiovascular residual que se observa en pacientes eficazmente tratados para reducir sus niveles de LDL; sin embargo, persiste el riesgo de ECA. Es imprescindible que en el estudio del perfil lipídico se considere la determinación o estimación de estas lipoproteínas, sumada a la medida de TG plasmáticos. El objetivo de la presente revisión fue actualizar el conocimiento acerca de los niveles incrementados de TG, de LRT y sus remanentes, brindar alternativas para su determinación y comprender los mecanismos que involucran a las LRT en el desarrollo acelerado de la aterosclerosis. La actualización de los diferentes parámetros asociados al aumento de TG y sus valores de corte o límites de decisión clínica según la clasificación del riesgo de ECA para cada paciente, permitirá el rediseño de un informe de resultados que será de gran utilidad para el médico y el paciente con respecto a las conductas preventivas y terapéuticas de la ECA.

Abstract Vast scientific evidence from clinical, preclinical, epidemiological, and genetic trial results show a causal association between increased triglycerides (TG), TG-rich lipoproteins (TRL), and their remnants for atherosclerotic cardiovascular disease (ASCVD). The accumulation of circulating LRT may explain, in part, the residual cardiovascular risk observed in patients successfully treated to reduce their LDL levels, however, the risk of ASCVD still persists. It is essential that in the assessment of the lipid profile, the determination or estimation of these lipoproteins be considered, added to the measurement of plasmatic TG. The objective of this review is to update the knowledge about the increased levels of TG, LRT and their remnants, proprovide alternatives for their determination and understand the mechanisms that involve LRT in the accelerated development of atherosclerosis. Updating the different parameters associated with increased TG and their cut-off values or clinical decision limits according to the ASCVD risk classification for each patient will allow for the redesign of a results report that will be very useful for the physician and the patient regarding the preventive and therapeutic behaviours of the ASCVD.

Resumo Vastas evidências científicas de resultados de ensaios clínicos, pré-clínicos, epidemiológicos e genéticos mostraram uma associação causal entre o aumento de triglicerídeos (TG), lipoproteínas ricas em TG (LRT) e seus remanescentes para doença cardiovascular aterosclerótica (DCA). O acúmulo de LRT circulante pode explicar, em parte, o risco cardiovascular residual observado em pacientes tratados de maneira eficaz para reduzir seus níveis de LDL, no entanto, o risco de DCA persiste. É fundamental que no estudo do perfil lipídico seja considerada a determinação ou estimativa dessas lipoproteínas, somada à dosagem de TG plasmáticos. O objetivo desta revisão foi atualizar o conhecimento sobre os níveis aumentados de TG, LRT e seus remanescentes, fornecer alternativas para sua determinação e compreender os mecanismos que envolvem as LRT no desenvolvimento acelerado da aterosclerose. A atualização dos diferentes parâmetros associados ao aumento de TG, e seus valores de corte ou limites de decisão clínica de acordo com a classificação do risco de DCE para cada paciente, permitirá o redesenho de um relatório de resultados que será muito útil para o médico e o paciente quanto às condutas preventivas e terapêuticas da DCE.

Analysis of Dyslipidemia as per Ayurveda and its Management

Dyslipidaemias refers to any abnormality in the level of circulating plasma lipids. It is an extremely significant condition, majorly because of its contribution to atherogenesis. It is an independent and modifiable risk factor for CAD and stroke. More than half of global cases of ischemic heart disease are associated with dyslipidemia. Quality of care for dyslipidemia is suboptimal in general and variable by cardiovascular disease risk group, ethnicity and gender. In modern medicine, there are effective dyslipidemic drugs which give rapid relief, but may cause some long term side effects. So there is a need for safe alternative treatment which may be effective in reducing lipid level, for prolonged use. In Ayurveda, dyslipidemia can be considered as a condition in which Kapha, Medas and Rasa are pathologically deranged due to Ama. There is defective Medo dhatu poshana due to Dhatwagnimandhya and formation of Ama at the level of Medo dhatu. It can be considered as presumable level of stage of Samprapti or a morbid state which may cause disease, but not attained a full status of disease. Nidanas include Beejadushti, Ahara – vihara –vikara and Manasika nidanas. Lipid profile can be brought back to normal by correcting Agni and ensuring proper Dhatuparinama. Treatment modalities include Nidana parivarjana, Sodhana, Samana, Rasayana and following Pathyapathya. Drug having Kaphamedohara, Deepana, Pachana, Ruksha and Lekhana property is useful to treat this clinical condition.

Tobacco Exposure and its Possible Electrocardiographic Changes in Female Beedi Rollers in Tirunelveli District

Introduction: Around 5 million female beedi workers in India are rolling beedi for 6–12 h and handling 225–450 g of beeditobacco/day in a poor household environment. Beedi tobacco dust gets absorbed through the cutaneous and pharyngealroute. Nicotine, the main component, is a potent cardiac myocyte, A-type potassium channel inhibitor. Nicotine, a potentarrhythmogenic agent, causes electrophysiological disturbances such as shortened QTc and prolonged T-wave end (Tp-e)interval, by prolonging ventricular repolarization time. Nicotine accelerates atherogenesis also. Very few Indian studies areavailable to highlight this aspect.Aim: This study aims to observe the electrocardiogram (ECG) changes in female beedi rollers in Tirunelveli district.Materials and Methods: The study population consisted of 35 female beedi rollers, aged between 20 and 50 years, rollingbeedi for at least 5 years. Blood pressure and ECGs were performed on all subjects following standard operating procedure.Heart rate, QTc, and Tp-e intervals were measured.Results: The mean age of beedi rollers is 45.75 ± 7.1 years with mean years of exposure of 19.70 ± 8.05 years rolling 22.8 ± 8.54beedi bundles/day. There is no correlation found in systolic and diastolic pressure. Mean QTc interval was 432 ± 23.6 ms, meanTp-e interval is 79.47 ± 3.2 ms; there is no correlation in the duration of beedi rolling with ECG parameters.Conclusion: Beedi tobacco (nicotine) exposure is associated with risk of accelerated atherogenesis and arrhythmogenesis,but in our study, beedi rollers are not showing changes in ECG.

Catechins green tea upregulates the expression of ABCA1, ABCG1, and SRB1 in rats induced atherogenic diet

The efflux of cholesterol from macrophage to liver is known as reverse cholesterol transport (RCT). Impairedcholesterol efflux leads to cholesterol accumulation in macrophages. Therefore, how to increasing cholesterol effluxmay be an effective strategy for atherosclerosis prevention. Key molecules that play a vital role in the efflux ofcholesterol from macrophage are Adenosin Tri Phosphate (ATP)-binding casette transporters A1 and G. This study wasundertaken to clarify the effect of Catechins on the expression of specific transporters such as ATP-binding cassettesub-family A member 1 (ABCA1), ATP-binding cassette sub-family G member 1 (ABCG1) from macrophage to liver,and scavenger receptor class B type I (SRB1). This research was done on Wistar rats induced atherogenic diets. SRB1is one of the transporters to facilitate the delivery of cholesterol from the macrophage to the liver. The SRB1 pathwaymediated the selective uptake of cholesteryl ester. Catechins significantly increased the mRNA expression of ABCA1and ABCG1 in aorta as well as SRB1 of liver also increased. Thus, Catechins decreased the total cholesterol levels inaorta and serum. Catechins can be developed as a potential agent to increase ABCA1 to inhibit atherogenesis process.In conclusion, this study indicates that the potential anti-atherogenic properties of Catechins could be explained, atleast in part, as being due to upregulated expression of ABCA1, ABCG1, and SRB1 through activation liver X receptorsignaling pathway

Catechins green tea upregulates the expression of ABCA1, ABCG1, and SRB1 in rats induced atherogenic diet

The efflux of cholesterol from macrophage to liver is known as reverse cholesterol transport (RCT). Impairedcholesterol efflux leads to cholesterol accumulation in macrophages. Therefore, how to increasing cholesterol effluxmay be an effective strategy for atherosclerosis prevention. Key molecules that play a vital role in the efflux ofcholesterol from macrophage are Adenosin Tri Phosphate (ATP)-binding casette transporters A1 and G. This study wasundertaken to clarify the effect of Catechins on the expression of specific transporters such as ATP-binding cassettesub-family A member 1 (ABCA1), ATP-binding cassette sub-family G member 1 (ABCG1) from macrophage to liver,and scavenger receptor class B type I (SRB1). This research was done on Wistar rats induced atherogenic diets. SRB1is one of the transporters to facilitate the delivery of cholesterol from the macrophage to the liver. The SRB1 pathwaymediated the selective uptake of cholesteryl ester. Catechins significantly increased the mRNA expression of ABCA1and ABCG1 in aorta as well as SRB1 of liver also increased. Thus, Catechins decreased the total cholesterol levels inaorta and serum. Catechins can be developed as a potential agent to increase ABCA1 to inhibit atherogenesis process.In conclusion, this study indicates that the potential anti-atherogenic properties of Catechins could be explained, atleast in part, as being due to upregulated expression of ABCA1, ABCG1, and SRB1 through activation liver X receptorsignaling pathway.

Highly Sensitive C - Reactive Protein In Hypertension, As A Potential Marker Of Cardiovascular Events A Case-control Hospital-based Study

As inflammation had a role in every stage of atherogenesis and hypertension, in turn leading to Cardiovascular Disease. Hs-CRP level estimation can be an important screening method for assessing the risk. Thus, this study to evaluate the effect of essential hypertension on hsCRP levels in Indian adult population. As well as clustering of other cardiovascular risk factors in comparison with a control group in a population. Acase-control study was carried out in of Era's Lucknow Medical College & Hospital, Lucknow, and Uttar Pradesh. All patients coming in out-patient department were screened for inclusion & exclusion criteria. Those selected were subjected to screening of risk factors of cardiovascular diseases & serum hs CRP estimation.Significant CAD risk factors in our cases came out to be: higher weight (p-value: 0.0470), raised BMI (>25) (p-value: 0.005), higher waist circumference (p-value: 0.0010) & smoking (p-value: 0.008). Average hs-CRP values in the hypertensive group (cases) was higher (2.85 ± 2.4 mg/L) than in normotensive group (control) (2.36 ± 2.08 mg/L). No significant difference in values among the controlled & uncontrolled group of previously diagnosed hypertensives was observed but a significant difference was found between newly diagnosed Stage I & Stage II hypertensives.Also, though not significant a rising trend was noted in hs-CRP values with an increase in the risk category. On CAD risk stratification according to hs CRPvalues cases hada significantly higher prevalence of hs-CRP levels than controls. Conclusion: The study did not reveal any significant difference in hs CRPvalues in hypertensives than from the normotensive population. But the significant difference between Stage I & Stage II of hypertension was observed in hs-CRPvalues.

Effect of agonist of angiotensin-(1-7) on atherogenesis in apolipoprotein E-knockout mice / 中华老年医学杂志

Objective To investigate the effects of agonist of angiotensin-(1-7)(AVE0991) on endothelial function and atherogenesis in apolipoprotein E knockout (ApoE-/-) mice.Methods Eight-week-old ApoE-/-male mice and C57BL/6J male mice were randomly divided into 3 groups:a normal diet control group(ND,n=10),a high-fat diet group(HFD,n=10),and a high-fat diet with AVE0991 0.58 μmol · kg-1 · d-1 group(HFD+ AVE0991,n=10).After 12 weeks of treatment,serum levels of lipids and parameters of endothelial function were measured.Atherosclerotic lesions in aorta roots were detected by Oil Red O staining.CD31 levels in the arterial intima were analyzed by immunohistochemistry.Results AVE0991 had no effects on blood lipids (P ＞ 0.05)but lowered serum levels of nitric oxide in high-fat diet mice(76.8±34.4 μmol/L vs.116.8±33.9 μmol/L,P＜0.05).Also,AVE0991 had no effects on the activity of serum nitric oxide synthase(19.5±5.7 U/ml vs.17.9±3.3 U/ml,P＞0.05)but decreased the activity of serum induced nitric oxide synthase(9.0 ±2.3 U/ml vs.12.7 ± 3.2 U/ml,P ＜0.05) and increased the ratio of phosphorylated endothelial nitric oxide synthase to induced nitric oxide synthase in the vessel wall in high-fat diet mice(0.8±0.2％ vs.0.6 ± 0.2％,P ＜ 0.05).AVE0991 decreased serum levels of C-reactive protein,tumor necrosis factor-α and interleukin-6 (P ＜ 0.05),and decreased the area percentage of atherosclerotic lesions in aorta roots (15.6 ± 3.3 ％ vs.45.4 ± 9.8 ％,P ＜ 0.05) and increased the integrated optical density of CD31 in the arterial intima in high-fat diet mice(54.1±11.0％ vs.28.7±10.6％,P＜0.05)Conclusions AVE0991 can attenuate atherogenesis in ApoE-/-mice fed a high-fat diet,possibly via reducing inflammatory response,regulating the activity of nitric oxide synthases and improving endothelial functions.

Effects of prolonged isolation in a confined space on status of oxidative stress and prothrombogenesis: In preparation for possible future manned space expedition to Mars

@#Introduction: Apart from inflammation and endothelial dysfunction, other key components in the development of atherogenesis include prothrombogenesis and oxidative stress. The effects of long-term confinement and isolation, exposure to radiation and different gravity forces during space travel could potentially increase the long-term risk of atherosclerosis. To the best of our knowledge, this is the first study determining the status of prothrombogenesis and oxidative stress in six cosmonauts subjected to the longest duration of confined isolation period of 520 days in preparation for prospective undetermined manned space travel to Mars. Materials and Methods: This collaborative research between the National Space Agency (ANGKASA), Universiti Teknologi MARA, Malaysia and Institute of Biomedical Problems (IBMP), Russia was conducted at the Russian Academy of Sciences IBMP, Moscow, Russia. Six multi-national cosmonauts were assigned to live in a ground-based confined module for 520 days. Standard exercise and diet regime were instituted throughout the isolation phase. Six age, ethnic and gender-matched healthy, free-living ground controls were recruited in parallel. Serial serum and whole blood were analysed for biomarkers of prothrombogenesis [plasminogen activator inhibitor-1 (PAI-1) and homocysteine] and oxidative stress [oxidised low-density lipoprotein (ox-LDL) and malondialdehyde (MDA)]. Results: There were significantly lower concentrations of PAI-1 and homocysteine in cosmonauts during confinement compared to the controls. There were no significant differences seen in the concentrations of biomarkers of oxidative stress during confinement but there was a significant percentage change increment for serum MDA in cosmonauts. Conclusion: Long-term confinement decreased the risk of prothrombogenesis and this could be attributed to the exercise and diet regime which includes omega-3 fatty acids supplementation given to the crew members during their confinement period. However, oxidative damage could not be excluded and may be attributed to the influence of psychological stress during this prolonged confinement.

The attempt to demolish the science and practice of preventive cardiovascular medicine. Part I. Addendum to the positioning around the diagnosis and treatment of dyslipidemias of ANCAM and the joint group of associated medical societies / El intento de demoler la ciencia y la práctica de la medicina cardiovascular preventiva. Parte I. Addendum al posicionamiento en torno al diagnóstico y tratamiento de las dislipidemias de la ANCAM y del grupo conjunto de sociedades médicas asociadas

Abstract: This manuscript is an addendum to the positioning around the diagnosis and treatment of dyslipidemias of ANCAM and the joint group of associated medical societies, already published. It is the first part of a wider reflection aimed on refute several of the theses and arguments of a group of clinicians and researchers who question the validity of the "cholesterol hypothesis", the usefulness and safety of statins and the most modern inhibitors of proprotein convertase of subtilisin/kexin type 9 (iPCSK9,) and the role of saturated fatty acids consumed in the usual diet in the atherosclerotic risk. This iconoclastic point of view is dangerous insofar as it undermines the scaffolding that supports the primary and secondary prevention of atherosclerosis. In this section of the manuscript, only the cholesterol hypothesis is discussed. The data of comparative zoology are reviewed, and several experimental animal models are analyzed, both supporting the link between cholesterol and the appearance and evolution of atherosclerotic lesions. The methodology and the results of the Study of the 7 Countries are defended and are exposed the numerous epidemiological, pathological, clinical and interventional evidences, which in our opinion give a solid sustenance to the cholesterol hypothesis. Based on this knowledge it is criticized the LDL cholesterol values currently considered adequate. Furthermore, the so-called residual risk is considered, as well as the conflicting evidence about the usefulness of statins in elderly patients.

Resumen: Este manuscrito es un apéndice del posicionamiento en torno al diagnóstico y tratamiento de las dislipidemias de la ANCAM y el grupo de las sociedades médicas asociadas, previamente publicado. Es la primera parte de un trabajo más amplio enfocado a refutar varias de las tesis y argumentos de un grupo de clínicos e investigadores que ponen en duda la validez de la "hipótesis del colesterol", la utilidad y seguridad de las estatinas y los más modernos inhibidores de la proproteína convertasa de la subtilisina/kexina tipo 9 (iPCSK9) y el papel de los ácidos grasos saturados consumidos en la dieta habitual en el riesgo ateroscleroso. Este punto de vista iconoclástico es peligroso porque socava el andamiaje que soporta la prevención primaria y secundaria de la aterosclerosis. En esta primera sección del manuscrito, se discute sólo la hipótesis del colesterol. Se revisan los datos de zoología comparada y se analizan varios modelos animales de experimentación, que apoyan la liga entre el colesterol y la aparición y evolución de las lesiones aterosclerosa. Se defienden la metodología y los resultados del estudio de los 7 países y se exponen las numerosas evidencias epidemiológicas, patológicas, clínicas e intervencionistas, que a nuestro juicio dan un sustento sólido a la hipótesis del colesterol. Se critican también, en base a ese conocimiento, los valores de colesterol LDL actualmente considerados adecuados, a la vez que se discute el llamado riesgo residual y las evidencias conflictivas acerca de la utilidad de las estatinas en pacientes ancianos.

Subclinical atherogenesis in patients with mild psoriasis: A role for IL-6? / Aterogênese subclínica em pacientes com psoríase leve: um papel para IL-6?

Summary Introduction: A link of psoriasis with subclinical atherosclerosis has been postulated and cytokine network might intermediate this association. Few data are available in patients with mild psoriasis. We evaluated carotid intima-media thickness (cIMT) in drug-free psoriatic individuals and controls. In parallel, we searched for associations of cIMT with disease activity indexes and serum interleukins (IL) in psoriatic patients. Method: An experienced radiologist performed the cIMT analyses. Cytokine concentrations were assessed by flow cytometry. Disease activity was evaluated based on psoriasis area and severity index (PASI) as well as body surface area (BSA). Results: Sixty-five (65) patients and 64 controls were studied. Mean age of patients (50.9 years) did not differ from controls (p=0.362). A low PASI and BSA (< 10) prevailed (69.2% and 56.9%, respectively). Median levels of IL-12p70, TNF-α, IL-1β and IL-10 were significantly lower in cases than in controls (adjusted p<0.05), while IL-6 and IL-8 medians did not differ between groups (adjusted p>0.05). Smoking habit and diabetes mellitus predominated in cases (p=0.002). An altered cIMT (≥ 0.9 mm) was more frequent in cases than in controls (23.8% versus 8.5%, adjusted p=0.045). Mean cIMT was higher in cases with a borderline significance (p=0.057). cIMT scores did not correlate to PASI (rs=0.066; p=0.250) or BSA (rs=0.175; p=0.185), but did correlate significantly with serum IL-6 (rs=0.26; p=0.005). Conclusion: Subclinical atherosclerosis was more frequent in patients with mild psoriasis than controls. cIMT in psoriatic individuals correlated with serum IL-6, pointing to an eventual proatherogenic role of IL-6 in these patients. Newer studies should clarify the connection of atherogenesis with cytokines in psoriasis.

Resumo Introdução: Foi postulada uma ligação entre psoríase e aterosclerose subclínica. A rede de citocinas pode intermediar essa associação. Poucos dados estão disponíveis em pacientes com psoríase leve. Avaliamos a espessura íntima-média carotídea (cIMT) em psoriáticos e controles livres de medicação. Paralelamente, pesquisamos a associação de cIMT com os índices de atividade de doença e interleucinas séricas (IL) em pacientes com psoríase. Método: Um radiologista experiente procedeu à análise do cIMT. As concentrações de citocinas foram avaliadas por citometria de fluxo. A atividade da doença foi avaliada pelo índice de gravidade (PASI) e pela área de superfície corporal (BSA). Resultados: Sessenta e cinco (65) pacientes e 64 controles foram estudados. A idade média dos pacientes (50,9 anos) não diferiu dos controles (p=0,362). PASI e BSA baixos (< 10) prevaleceram (69,2% e 56,9%, respectivamente). As medianas de IL-12p70, TNF-α, IL-1β e IL-10 foram significativamente menores nos casos do que nos controles (p<0,05 ajustado), enquanto as medianas de IL-6 e IL-8 não diferiram nos grupos (p>0,05 ajustado). Tabagismo e diabetes mellitus predominaram nos casos (p=0,002). Um cIMT alterado (≥ 0,9 mm) foi mais frequente nos casos do que nos controles (23,8% versus 8,5%, p=0,045 ajustado). A média de cIMT foi maior nos casos com significância borderline (p=0,057). Os escores de cIMT não se correlacionaram com o PASI (rs=0,066; p=0,250) ou o BSA (rs=0,175; p=0,185), mas se correlacionaram significativamente com a IL-6 sérica (rs=0,26; p=0,005). Conclusão: A aterosclerose subclínica foi mais frequente em pacientes com psoríase leve do que nos controles. Em psoriáticos, cIMT correlacionou-se com níveis de IL-6 no soro, apontando para um eventual papel pró-aterogênico para a IL-6 nesses pacientes. Novos estudos devem esclarecer a ligação da aterogênese com citocinas na psoríase.

Nikolai Anichkov y los cien años de la hipótesis sobre el colesterol y la aterogénesis / Nikolai Anichkov and one hundred years of the hypothesis about cholesterol and atherogenesis

The relationship of cholesterol to atherogenesis already fulfilled one hundred years. The merit of this important discovery is attributed to a Russian military doctor, Nikolai Anichkov, who using rabbits as experimental model, was able to show the accumulation of "lipoids" when he fed animals with a diet rich in cholesterol. His experimental observations were criticized by many researchers, since he used an animal that is not carnivorous, so it was an inappropriate model. Anichkov published very few scientific articles, and all of them in Russian language. Only in 1933 he could make public his work to the Western world by publishing a review on his scientific work in English. Was only in 1984 when the scientific community recognized the merit of his research, which was pioneer in the understanding that we have today about the relationship of artherogenesis and cholesterol.

La relación del colesterol con la aterogénesis ya cumplió cien años. El mérito de este importante descubrimiento lo tiene un médico militar ruso Nikolai Anichkov, quien utilizando conejos como modelo experimental, pudo demostrar la acumulación de "lipoides" cuando los alimentaba con una dieta rica en colesterol. Sus observaciones fueron criticadas por numerosos investigadores ya que utilizaba un animal que no es carnívoro, por lo cual era un modelo inadecuado. Anichkov publicó muy pocos trabajos científicos y todos ellos en idioma ruso. Solo en 1933 pudo hacer público su trabajo al mundo occidental al publicar en inglés una revisión sobre su trabajo científico. Tardíamente, en 1984, se reconoció por parte de la comunidad científica el mérito de su investigación, la que fue pionera en la comprensión que tenemos hoy día sobre la enfermedad arterioesclerótica y el colesterol.

Circulating early biomarkers of atherogenesis in participants of the Longitudinal Study of Adult Health (ELSA-Brasil) without diabetes or cardiovascular disease

ABSTRACT Objective Our aim was to describe the distribution of selected biomarkers according to age and sex, adjusted for HOMA-IR and adiposity, in a subset of middle-aged individuals of Brazilian Longitudinal Study of Adult Health-ELSA without diabetes mellitus or CVD. Subjects and methods This cross-sectional study was conducted in 998 participants of the ELSA-Brasil without diabetes and/or cardiovascular disease. In addition to the traditional risk factors, several biomarkers concentrations were compared according to sex, age groups (35-44; 45-54 yrs) and HOMA-IR tertiles. Linear regression was used to examine independent associations of sex and age with selected novel biomarkers, adjusted for body adiposity and HOMA-IR. Results Fifty-five percent were women. Men had higher mean values of body mass index, waist circumference, blood pressure, plasma glucose, HOMA-IR, worse lipid profile and higher E-selectin and lower leptin concentrations than women; while women had higher levels of HDL-cholesterol and leptin than men. Mean values of waist circumference, systolic BP, plasma glucose and apolipoprotein B (Apo B) increased with age in both sexes. Leptin and E-selectin concentrations increased across HOMA-IR tertiles. Independent associations of Apo B with age were found only in male sex, while of leptin with body mass index and HOMA-IR, and of E-selectin with HOMA-IR in both sexes. Conclusions In conclusion, our data indicate age, sex, adiposity and, consequently, insulin resistance, influence circulating levels of Apo B, leptin and E-selectin, suggesting that those aspects should be taken into consideration when assessing these parameters for research or clinical purposes in individuals at relatively low cardiometabolic risk.

Synergism of Malnutrition, Inflammation and Fluid Load in the Development of Atherogenesis in Uremic Patients Undergoing Peritoneal Dialysis.

Objective: Approximately 50% of end stage renal disease (ESRD) patients lose their lives as a consequence of cardiovascular diseases due to accelerated atherosclerosis. The objectives of this study were to investigate the synergistic effect between nutritional status, inflammation and volume load with atherogenesis estimated using structural and hemodynamic changes in the carotid arteries (CA) in patients on peritoneal dialysis (PD). Methods: Prospective longitudinal study. The study sample consisted of 50 ESRD patients who were treated with PD and were observed for an 18 months after the commencement of dialysis treatment. All examined patients underwent 4 to 5 dialysis changes with 2 liters of dialysis solution. The laboratory findings were complemented with ultrasound of CA and echocardiography at baseline and at the end of follow-up. Results: C-reactive protein (CRP), B-type natriuretic peptide and homocysteine significantly were significantly decreased, while normal protein nitrogen appearance (nPNA) and albumin values were significantly increased after 18 months on PD. The carotid intima-media thickness (CIMT), left atrium diameter was significantly decreased (p<0.001) at the end of the study. Significant predictors of CIMT and CA diameter were residual renal function (RRF), albumin and CRP whereas significant predictors of presence of atherosclerotic plaques were RRF and CRP. Conclusion: We have found a close relationship between hemodynamic and structural CA changes with markers of poor nutrition, inflammation and hydration status in PD patients. The synergism of atherogenesis and monitored parameters, especially CA diameter and CIMT, seems to be useful in the management of PD patients and deserves further testing in properly designed clinical validation study.

Do parental coronary heart disease risk factors (non-modifiable) effect their young ones?

Objective: To study the differences between the lipid profiles of the subjects whose parents are having known non-modifiable risk factors such as obesity, hypertension (HTN), myocardial infarction and diabetes, and compare them with the lipid profiles of the subjects whose parents are not having those risk factors. Methods: A total of 402 subjects were recruited to this study. A detailed questionnaire which included information on the past medical history, height, weight, blood pressure, physical activity, smoke, alcohol, family history of coronary heart disease, HTN, diabetics and obesity. Basic demographic data and dietary habits were completed by all participants. Blood samples were obtained from all subjects after 14 h. Lipid profiles were analyzed using automated analyzer. The results were analyzed using SPSS software packages. Results: The mean body mass index of the population was well below the cut-off value of obesity (>24.5 kg/m

Atorvastatin inhibits atherogenesis by RXRα-mediated depressing oxida-tive stress in STZ-induced diabetic ApoE-/-mice with fat-rich diet / 中国病理生理杂志

AIM:To explore the effects of atorvastatin (Atorv) on atherosclerosis in streptozotocin (STZ)-in-duced diabetic apolipoprotein E knockout ( ApoE-/-) mice with fat-rich diet and the possible mechanism .METHODS:C57 mice served as control.ApoE-/-mice (n=34) fed with high-fat diet were randomly divided into ApoE-/-group, STZ-ApoE-/-group and STZ-ApoE-/-+Atorv group.Intraperitoneal injection of streptozotocin was performed to create di-abetic animal model .Blood glucose was determined by glucose oxidase method .Blood lipid levels were detected by enzymic method or selective homogeneous method .The plaque area in the thoracic aorta was measured by HE staining .The protein level of nicotinamide-adenine dinucleotide phosphate ( NADPH) oxidase subunit gp91phox in the thoracic aorta was deter-mined by Western blotting .The levels of reactive oxygen species ( ROS) in blood and thoracic aorta homogenates were de-tected by Fenton reaction and Griess reagent .Human umbilical vein endothelial cells ( HUVECs ) were isolated from healthy umbilical cords by collagenase I and cultured .ROS production was detected by flow cytometry .NADPH oxidase ac-tivity was measured using lucigenin assay .Effects of retinoid X receptor α( RXRα) on inhibition of oxidative stress by ator-vastatin were evaluated by RNA interference and plasmid transfection .RESULTS: (1) Compared with C57 group, the plaque areas of the thoracic aorta in ApoE-/-group were increased .No difference of the fasting glucose between the 2 groups was observed.The levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), thoracic aorta gp91phox protein and ROS in blood and thoracic aorta homogenates were higher in ApoE-/-group than those in C57 group.(2) Compared with ApoE-/-group, the plaque areas of the thoracic aorta in STZ-ApoE-/-group were further enlarged [(314.13 ±35.72) μm2 vs (215.88 ±34.19) μm2, P<0.05].The levels of blood glucose, TG, TC and LDL-C, thoracic aorta gp91phox protein and ROS in blood and thoracic aorta homogenates were higher in STZ-ApoE-/-group than those in ApoE-/-group (P<0.05).(3) Compared with STZ-ApoE-/-group, the plaque areas of the thoracic aorta in STZ-ApoE-/-+Atorv group were reduced [(217.47 ±24.56) μm2 vs (314.13 ±35.72) μm2, P<0.05].The levels of blood glucose , LDL-C, TC, HDL-C and TG showed no significant difference between the 2 groups.Thoracic aorta gp91phox protein level and ROS production in blood and thoracic aorta homogenates were lower in STZ -ApoE-/-+Atorv group than those in STZ-ApoE-/-group (P<0.05).(4) High glucose-induced increases in NADPH oxidase activity and gp91phox expression were significantly inhibited by atorvastatin (10-6 mol/L) in HUVECs.The inhibitory effects of atorvasta-tin on high glucose-induced ROS production and NADPH oxidase activation were largely impaired when the cells were trans -fected with RXRαsiRNA.However , the effect of atorvastatin was significantly strengthened when RXRαwas over-expressed in the HUVECs transfected with RXRαplasmid.CONCLUSION: Atorvastatin inhibits atherogenesis by depressing high glucose-induced oxidative stress in diabetic ApoE-/-mice with fat-rich diet.The anti-oxidative stress effect of atorvastatin is mediated by RXRα.

Effects of Emblica Officinalis (AMLA) on Serum Lipids and Atherogenesis in Albino Rats Fed with High Fat Diet.

Objective: To evaluate the effects of Emblica officinalis (Amla) extract on serum lipids and atherogenesis, in albino rats fed with high fat diet. Materials and Methods: Healthy albino rats of Wistar strain (150-200 gm each) were randomized into five groups of six animals each- Group A (received normal diet), Group B (received normal diet + Emblica officinalis extract 1 gm/kg BW) Group C (received high fat diet consisting of vanaspati ghee and coconut oil at a ratio of 3:2, at a dose of 10 ml/kg/day), Group D (received high fat diet + Emblica officinalis extract 1 gm/kg BW) and Group E (received high fat diet + simvastatin 1.8 mg/ kg BW). Treatment period was 8 weeks. At the end of 8 weeks, lipid profile was evaluated by estimating total cholesterol, serum triglyceride, serum LDL, serum HDL and atherogenic index. Results: Ethanolic extract of Emblica officinalis showed significant antihyperlipidaemic activity (P< 0.01) with significant improvement in atherogenic index (p<0.01). Conclusion: Present study suggests that Emblica officinalis extract at a dose of 1 gm/kg BW exerts antihyperlipidaemic effect comparable to that of simvastatin. It also possesses hypolipidaemic activity.

Increased levels of Porphyromonas gingivalis are associated with ischemic and hemorrhagic cerebrovascular disease in humans: an in vivo study

OBJECTIVE: This study investigated the role of periodontal disease in the development of stroke or cerebral infarction in patients by evaluating the clinical periodontal conditions and the subgingival levels of periodontopathogens. MATERIAL AND METHODS: Twenty patients with ischemic (I-CVA) or hemorrhagic (H-CVA) cerebrovascular episodes (test group) and 60 systemically healthy patients (control group) were evaluated for: probing depth, clinical attachment level, bleeding on probing and plaque index. Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans were both identified and quantified in subgingival plaque samples by conventional and real-time PCR, respectively. RESULTS: The test group showed a significant increase in each of the following parameters: pocket depth, clinical attachment loss, bleeding on probing, plaque index and number of missing teeth when compared to control values (p<0.05, unpaired t-test). Likewise, the test group had increased numbers of sites that were contaminated with P. gingivalis (60 percentx10 percent; p<0.001; chi-squared test) and displayed greater prevalence of periodontal disease, with an odds ratio of 48.06 (95 percent CI: 5.96-387.72; p<0.001). Notably, a positive correlation between probing depth and the levels of P. gingivalis in ischemic stroke was found (r=0.60; p=0.03; Spearman's rank correlation coefficient test). A. actinomycetemcomitans DNA was not detected in any of the groups by conventional or real-time PCR. CONCLUSIONS: Stroke patients had deeper pockets, more severe attachment loss, increased bleeding on probing, increased plaque indexes, and in their pockets harbored increased levels of P. gingivalis. These findings suggest that periodontal disease is a risk factor for the development of cerebral hemorrhage or infarction. Early treatment of periodontitis may counteract the development of cerebrovascular episodes.