Impacto del COVID-19 en las enfermedades hepáticas y la salud pública en el Perú / Impact of COVID-19 on liver disease and the public health in Peru

RESUMEN La pandemia declarada por la OMS originada por el COVID-19 (enfermedad infecciosa originada por el virus SARS-CoV2), desde su aparición en Wuhan, China en diciembre 2019; esta diseminándose rápidamente y de manera inesperada por todo el mundo originando millones de casos y miles de muertes, afectando más de 120 países y desde el 06 marzo 2020 al Perú, distribuyéndose rápidamente por todo el país, originando crisis y colapso del sistema de servicios de salud, especialmente de las atenciones en emergencia, hospitalizaciones y unidades de cuidados intensivos abarrotadas; sin tener aún un tratamiento específico ni la posibilidad de una vacuna a corto plazo. Se sabe actualmente que COVID-19, es una enfermedad sistémica que puede afectar múltiples órganos y tejidos y que puede ser fatal. El objetivo de esta revisión es mostrar lo descrito en los recientes estudios publicados a nivel mundial incluido nuestro país, que han reportado sus manifestaciones clínicas, esbozando posibles mecanismos de disfunción hepática relacionados a COVID-19 y sus repercusiones, en especial sobre el aparato digestivo; analizando y discutiendo el potencial impacto sobre ellas y las enfermedades del hígado, enunciando las recomendaciones de expertos y organizaciones científicas respecto a medidas de prevención, control y manejo, además de esbozar algunas estrategias de salud pública en nuestro país para la adecuada atención de estos pacientes en tiempos de crisis generalizada.

ABSTRACT The pandemic of COVID-19 (an infectious disease caused by the SARS-CoV2 virus), declared as such by the WHO, is spreading since its appearance in Wuhan (China) in December 2019, rapidly and unexpectedly throughout the world, causing millions of cases and thousands of deaths and has affected more than 120 countries. It was officially acknowledged in Peru on March 6th, 2020, and has spread rapidly throughout the country, causing first the crisis and then the collapse of the healthcare system, especially emergency care, admissions, and overcrowded intensive care units, not having a specific treatment or the foreseeable possibility of a short-term vaccine. COVID-19 is currently known for being a systemic disease that can affect multiple organs and tissues and can be fatal. The goal of this review is to present what has been described in recent studies, published worldwide and including our country, that have reported clinical manifestations, outlining possible mechanisms of liver dysfunction related to COVID-19 and its repercussions, especially on the digestive system. These studies analyze and discuss the potential impact on liver diseases, offering recommendations of experts and scientific organizations regarding prevention, control and management measures, outlining also some public health strategies in our country for the proper care of COVID-19 patients in times of widespread crisis.

Evaluation of renin and angiotensin II levels in pseudoexfoliation syndrome / Avaliação dos níveis de renina e angiotensina II na síndrome de pseudo-exfoliação

ABSTRACT Purpose: Pseudoexfoliation syndrome has been linked to impaired function of the heart and blood vessels. We conducted a study to investigate the role of the renin-angiotensin system in the etiopathogenesis of pseudoexfoliation syndrome. Methods: The subjects were 14 patients with pseudoexfoliation syndrome and 14 healthy controls who underwent cataract extraction. Preoperative 5-ml samples of peripheral venous blood and perioperative aqueous humor were collected from the patients in both groups. Plasma and aqueous humor renin levels were analyzed by an immunoradiometric method, and angiotensin II levels were analyzed by radioimmunassay. SPSS version 16.0 was used for statistical analyses. A p-value <0.05 was considered to indicate a statistically significant difference. Results: The mean ages of the patients in pseudoexfoliation and control groups were 71.7 ± 7.1 and 67.4 ± 9.3 years, respectively (p=0.140). The median aqueous humor renin level was 7.73 pg/ml (4.15-21) in the control group and 11.95 pg/ml (3.75-18.54) in pseudoexfoliation group (p=0.022). There were no differences between the two groups in the plasma renin, plasma angiotensin II, or aqueous humor angiotensin II levels. The correlations between plasma and aqueous humor renin levels and between plasma and aqueous humor angiotensin II levels were examined separately for each group; no significant correlations were observed in pseudoexfoliation group (r=-0.440, p=0.115; r=-0.414, p=0.142) or the control group (r=-0.232, p=0.425; r=0.482, p=0.081). Conclusion: Aqueous humor renin levels are higher in pseudoexfoliation syndrome. The results indicate a probable role of renin-angiotensin system in pseudoexfoliation syndrome. Further studies with larger numbers of cases are needed to clarify the precise association of renin-angiotensin system with the etiopathogenesis of pseudoexfoliation syndrome.

RESUMO Objetivo: A síndrome de pseudo-exfoliação tem sido associada ao comprometimento da função do coração e dos vasos sanguíneos. Foi realizado um estudo para investigar o papel do sistema renina-angiotensina na etiopatogenia da síndrome de pseudo-exfoliação. Métodos: Os sujeitos foram 14 pacientes com síndrome de pseudo-exfoliação e 14 controles saudáveis submetidos à extração de catarata. Amostras pré-operatórias de 5 ml de sangue venoso periférico e humor aquoso perioperatório foram coletadas dos pacientes em ambos os grupos. Os níveis de renina no plasma e humor aquoso foram analisados pelo método imunorradiométrico e os níveis de angiotensina II foram analisados por radioimunoensaio. O SPSS versão 16.0 foi utilizado para análises estatísticas. Considerou-se o valor de p<0,05 para indicar uma diferença estatisticamente significativa. Resultados: A média de idade dos pacientes nos grupos pseudo-exfoliação e controle foi de 71,7 ± 7,1 e 67,4 ± 9,3 anos, respectivamente (p=0,140). O nível médio de renina no humor aquoso foi de 7,73 pg / ml (4,15-21) no grupo controle e 11,95 pg/ml (3,75-18,54) no grupo pseudo-exfoliação (p=0,022). Não houve diferenças entre os dois grupos de renina plasmática, angiotensina II plasmática ou nos níveis de angiotensina II em humor aquoso. As correlações entre os níveis de renina no plasma e no humor aquoso e entre os níveis de angiotensina II no plasma e humor foram examinadas separadamente para cada grupo; n]ao foram observadas correlações significativas no grupo pseudo-exfoliação (r=-0,440, p=0,115; r=-0,414, p=0,142) ou no grupo controle (r=-0,232, p=0,425; r=0,482, p=0,081). Conclusão: Os níveis de renina no humor aquoso são mais elevados na síndrome de pseudo-exfoliação. Os resultados indicam um provável papel do sistema renina-angiotensina na síndrome de pseudo-exfoliação. Novos estudos com maior número de casos são necessários para esclarecer a associação precisa do sistema renina-angiotensina com a etiopatogenia da síndrome de pseudo-exfoliação.

AT2R (Angiotensin AT2 Receptor) Agonist, Compound 21, Prevents Abdominal Aortic Aneurysm Progression in the Rat.

The effects of the selective AT2R (angiotensin AT2 receptor) agonist, Compound 21 (C21), on abdominal aortic aneurysm formation were investigated in normotensive Wistar rats. Abdominal aortic aneurysm was induced by perfusion of isolated aortic segments with elastase. Treatment with C21 (0.03 mg/kg daily) was started after operation and continued for 14 days. Sham-operated animals and vehicle-treated animals after aneurysm induction served as controls. Aortic diameter, aortic wall distensibility, and pulse propagation velocity were measured via ultrasound. Hemodynamic parameters, aortic tissue protein expression, and serum cytokines were analyzed. On day 14 post aneurysm induction, aortic diameter of vehicle-treated animals was increased 1.6-fold compared with sham-operated rats (2.65±0.05 versus 1.70±0.06 mm; P<0.0001). C21 decreased aortic diameter in comparison to vehicle (1.9±0.06 versus 2.65±0.05; P<0.0001). Infrarenal blood velocity and aortic distensibility were reduced, whereas aortic wall stiffness was increased post aneurysm induction. These alterations were significantly ameliorated by treatment with C21 while blood pressure and cardiac contractility remained unchanged. Protein expression of IL-1ß (interleukin-1ß), NFκB (nuclear factor κB), MMP9 (matrix metalloproteinase 9), TGF-ß1 (transforming growth factor-ß1), and MLKL (mixed lineage kinase domain-like) in the aorta was significantly ( P<0.05) down-regulated in the C21 group compared with vehicle. Serum concentration of TGF-ß1 was decreased by C21 in comparison to vehicle ( P<0.01). AT2R stimulation with C21 prevented extracellular matrix degradation, maintained vascular integrity of the aorta and prevented abdominal aortic aneurysm progression.

Brain renin-angiotensin system: a potential therapeutic target for ischemic stroke / 国际脑血管病杂志

Brain renin-angiotensin system (RAS) is closely associated with many pathophysiological processes of cardiocerebrovascular diseases,including stroke.The activation of the different components in RAS will produce specific biological effects.This article reviews the roles of brain RAS in the pathophysiological processes of ischemic stroke,especially the neuroprotective effect of ACE2/Ang-(1-7)/Mas axis.

Angiotensin II type 2 receptor- and acetylcholine-mediated relaxation: essential contribution of female sex hormones and chromosomes.

Angiotensin-induced vasodilation, involving type 2 receptor (AT2R)-induced generation of nitric oxide (NO; by endothelial NO synthase) and endothelium-derived hyperpolarizing factors, may be limited to women. To distinguish the contribution of female sex hormones and chromosomes to AT2R function and endothelium-derived hyperpolarizing factor-mediated vasodilation, we made use of the four-core genotype model, where the testis-determining Sry gene has been deleted (Y(-)) from the Y chromosome, allowing XY(-) mice to develop a female gonadal phenotype. Simultaneously, by incorporating the Sry gene onto an autosome, XY(-)Sry and XXSry transgenic mice develop into gonadal male mice. Four-core genotype mice underwent a sham or gonadectomy (GDX) operation, and after 8 weeks, iliac arteries were collected to assess vascular function. XY(-)Sry male mice responded more strongly to angiotensin than XX female mice, and the AT2R antagonist PD123319 revealed that this was because of a dilator AT2R-mediated effect occurring exclusively in XX female mice. The latter could not be demonstrated in XXSry male and XY(-) female mice nor in XX female mice after GDX, suggesting that it depends on both sex hormones and chromosomes. Indeed, treating C57bl/6 GDX male mice with estrogen could not restore angiotensin-mediated, AT2R-dependent relaxation. To block acetylcholine-induced relaxation of iliac arteries obtained from four-core genotype XX mice, both endothelial NO synthase and endothelium-derived hyperpolarizing factor inhibition were required, whereas in four-core genotype XY animals, endothelial NO synthase inhibition alone was sufficient. These findings were independent of gonadal sex and unaltered after GDX. In conclusion, AT2R-induced relaxation requires both estrogen and the XX chromosome sex complement, whereas only the latter is required for endothelium-derived hyperpolarizing factors.

Effect of long-acting nitrate on expression of Ang Ⅱ receptor subtypes in kidneys of heart failure rats / 中华老年心脑血管病杂志

Objective To study the effect of long‐acting nitrate on cardiac function and expression of AngⅡreceptor (ATR)subtypes in kidneys of chronic heart failure (CHF)rats after myocardial infarction .Methods Ninety male Wistar rats aged 10 weeks were randomly divided into control group (group A ,n=9) ,sham operation group (group B ,n=8) ,HF model group (group C ,n=9) , low Elantan dose group (group D ,n=9) ,high Elantan dose group (group E ,n=9) ,olmesartan group (group F ,n=9) ,and combined high Elantan dose and olmesartan group (group G ,n=8) .A HF model was established by ligating the left anterior descending artery .The animals received gastric drugs for 6 weeks .Their cardiac function was assyed by ultrasound echocardiography and expressions of AT1 R and AT2 R were detected by RT‐PCR and Western blot ,respectively .Results The PRA and AngⅡexpression levels were significantly higher ,the AT1 R expression level was significantly higher and the AT2 R expression level was significantly lower in group C than in group B (P<0 .01 ,P<0 .05) .The PRA and AngⅡexpression levels were significantly lower ,the AT1 R expression level was significantly lower and the AT2 R expression level was significantly higher in groups E‐G than in group C (P<0 .05 ,P<0 .01) .The receptor expression levels were much higher in group G than in group F (P<0 .05) .Conclusion Long‐term use of long‐acting nitrate can effectively improve cardiac function and protect renal function .

Association of polymorphisms in angiotensin Ⅱ receptor gene with primary aldosteronism / 中国基层医药

Objective To investigate the relationship between the polymorphisms of angiotensin Ⅱ receptor gene and the risk of primary aldosteronism (PA).Methods Polymerase chain reaction -restriction fragment length polymorphism (PCR -RFLP)was used to examine the 1 1 66A /C polymorphism of AT1 R gene and 1 675A /G poly-morphism of AT2R gene in 85 patients with PA and 1 00 healthy controls.Results There was no significant difference of AT1 R 1 1 66A /C genotypes (AA,AC,CC)and allele (A and C)frequency among patients and controls (χ2 =0.430,P =0.806).There was obvious difference of AT2R 1 675A /G genotypes (AA,AG,GG)and allele (A and G) frequency among two groups (χ2 =6.1 21 ,P =0.01 3).The G allele was higher than A allele in PA group (χ2 =6.767,P =0.009).Conclusion Homogenic mutation of 1 675A /G site in AT2R gene may be one of risk factors of PA.

Angiotensin type 2 receptor stimulation increases renal function in female, but not male, spontaneously hypertensive rats.

Accumulating evidence suggests that the protective pathways of the renin-angiotensin system are enhanced in women, including the angiotensin type 2 receptor (AT2R), which mediates vasodilatory and natriuretic effects. To provide insight into the sex-specific ability of pharmacological AT2R stimulation to modulate renal function in hypertension, we examined the influence of the AT2R agonist, compound 21 (100-300 ng/kg per minute), on renal function in 18- to 19-week-old anesthetized male and female spontaneously hypertensive rats. AT2R stimulation significantly increased renal blood flow in female hypertensive rats (PTreatment<0.001), without influencing arterial pressure. For example, at 300 ng/kg per minute of compound 21, renal blood flow increased by 14.3±1.8% from baseline. Furthermore, at 300 ng/kg per minute of compound 21, a significant increase in urinary sodium excretion was observed in female hypertensive rats (+180±59% from baseline; P<0.05 versus vehicle-treated rats). This was seen in the absence of any major change in glomerular filtration rate, indicating that the natriuretic effects of AT2R stimulation were likely the result of altered renal tubular function. Conversely, we did not observe any significant effect of AT2R stimulation on renal hemodynamic or excretory function in male hypertensive rats. Finally, gene expression studies confirmed greater renal AT2R expression in female than in male hypertensive rats. Taken together, acute AT2R stimulation enhanced renal vasodilatation and sodium excretion without concomitant alterations in glomerular filtration rate in female hypertensive rats. Chronic studies of AT2R agonist therapy on renal function and arterial pressure in hypertensive states are now required to establish the suitability of AT2R as a therapeutic target for cardiovascular disease, particularly in women.

Effects of cardiac overexpression of the angiotensin II type 2 receptor on remodeling and dysfunction in mice post-myocardial infarction.

The activation of angiotensin II type 2 receptor (AT2R) has been considered cardioprotective. However, there are controversial findings regarding the role of overexpressing AT2R in the heart. Using transgenic mice with different levels of AT2R gene overexpression in the heart (1, 4, or 9 copies of the AT2R transgene: Tg1, Tg4, or Tg9), we studied the effect of AT2R overexpression on left ventricular remodeling and dysfunction post-myocardial infarction (MI). Tg1, Tg4, Tg9, and their wild-type littermates were divided into (1) sham MI, (2) MI plus vehicle, and (3) MI plus AT2R antagonist. Treatments were started 4 weeks after MI and continued for 8 weeks. AT2R protein and mRNA expression in the heart was significantly increased in transgenic mice, and the increase positively correlated with copies of the transgene. AT1R protein and mRNA expression remained unchanged in Tg1 and Tg4 but slightly increased in Tg9 mice. Systolic blood pressure and cardiac phenotypes did not differ among strains under basal conditions. MI caused myocardial hypertrophy, interstitial fibrosis, ventricular dilatation, and dysfunction associated with increased protein expression of Nox2 and transforming growth factor ß1. These pathological responses were diminished in Tg1 and Tg4 mice. Moreover, the protective effects of AT2R were abolished by AT2R antagonist and also absent in Tg9 mice. We thus conclude that whether overexpression of AT2R is beneficial or detrimental to the heart is largely dependent on expression levels and possibly via regulations of Nox2 and transforming growth factor ß1 signaling pathways.

Angiotensin type 2 receptor stimulation ameliorates left ventricular fibrosis and dysfunction via regulation of tissue inhibitor of matrix metalloproteinase 1/matrix metalloproteinase 9 axis and transforming growth factor ß1 in the rat heart.

Left ventricular (LV) remodeling is the main reason for the development of progressive cardiac dysfunction after myocardial infarction (MI). This study investigated whether stimulation of the angiotensin type 2 receptor is able to ameliorate post-MI cardiac remodeling and what the underlying mechanisms may be. MI was induced in Wistar rats by permanent ligation of the left coronary artery. Treatment with the angiotensin type 2 receptor agonist compound 21 (0.03 mg/kg) was started 6 hours post-MI and continued for 6 weeks. Hemodynamic parameters were measured by echocardiography and intracardiac catheter. Effects on proteolysis were studied in heart tissue and primary cardiac fibroblasts. Compound 21 significantly improved systolic and diastolic functions, resulting in improved ejection fraction (71.2±4.7% versus 53.4±7.0%; P<0.001), fractional shortening (P<0.05), LV internal dimension in systole (P<0.05), LV end-diastolic pressure (16.9±1.2 versus 22.1±1.4 mm Hg; P<0.05), ratio of early (E) to late (A) ventricular filling velocities, and maximum and minimum rate of LV pressure rise (P<0.05). Compound 21 improved arterial stiffness parameters and reduced collagen content in peri-infarct myocardium. Tissue inhibitor of matrix metalloproteinase 1 was strongly upregulated, whereas matrix metalloproteinases 2 and 9 and transforming growth factor ß1 were diminished in LV of treated animals. In cardiac fibroblasts, compound 21 initially induced tissue inhibitor of matrix metalloproteinase 1 expression followed by attenuated matrix metalloproteinase 9 and transforming growth factor ß1 secretion. In conclusion, angiotensin type 2 receptor stimulation improves cardiac function and prevents cardiac remodeling in the late stage after MI, suggesting that angiotensin type 2 receptor agonists may be considered a future pharmacological approach for the improvement of post-MI cardiac dysfunction.

Roles of angiotensin Ⅱ receptors in tumor / 国际肿瘤学杂志

Angiotensin (Ang Ⅱ),a main effector peptide of the renin-angiotensin system (RAS),mediates a hormonal action in the maintenance of blood pressure and electrolyte levels,and thus fluid homeostasis.Recent studies have implicated that it correlates with tumor growth,angiogenesis,metastasis and it has drawn more and more attention.Many studies show that Ang Ⅱ-AT1R/AT2R play crucial roles in tumor growth,metastasis,invasion and tumor angiogenesis,which are formed new targets for treating malignant tumors.

Amplification of recombinant adenovirus vector carrying rat angiotensinⅡtype 2 receptor and transfection in INS-1 cells / 军事医学

Objective To amplify the recombinant adenovirus vector carrying rat angiotensin Ⅱ type 2 receptor (AT2R) gene using human embryonic kidney (HEK) 293A cell lines and to construct a pancreatic islet βcell model overexpressing AT2R by transfecting the adenovirus vector into rat insulinoma (INS-1) cell lines.Methods Recombinant adenovirus vector Ad-G-AT2R-EGFP and control vector Ad-CMV-EGFP were amplified with HEK 293A cells and the titer of the adenovirus was detected .After both adenovirus vectors were transfected into INS-1 cells,AT2R and angiotensin Ⅱtype 1 receptor(AT1R) gene expressions were tested using real-time PCR, Western blotting, immunofluorescence staining and confocal laser-scanning microscopy .Results The titer of amplified Ad-G-AT2R-EGFP and Ad-CMV-EGFP was re-spectively 9 ×109 pfu/ml and 8 ×109 pfu/ml.Transfection of Ad-G-AT2R-EGFP into INS-1 cells induced an increase in AT2R mRNA expression in a dose-dependent manner , and significantly increased AT2R mRNA and protein expression compared with Ad-CMV-EGFP-or mock-transfection.Conclusion The recombinant adenoviral vector carrying AT2R gene is successfully amplified and an INS-1 cell model overexpressing AT2R is constructed by transient transfection , which can contribute to further study of the role of AT2R in pancreatic islet βcells.

Angiotensin II type 2 receptor-mediated and nitric oxide-dependent renal vasodilator response to compound 21 unmasked by angiotensin-converting enzyme inhibition in spontaneously hypertensive rats in vivo.

Angiotensin II type 2 receptor (AT2R)-mediated vasodilation has been demonstrated in different vascular beds in vitro and in perfused organs. In vivo studies, however, consistently failed to disclose renal vasodilator responses to compound 21, a selective AT2R agonist, even after angiotensin II type 1 receptor blockade. Here, we investigated in vivo whether angiotensin-converting enzyme inhibition, reducing endogenous angiotensin II levels, could unmask the effects of selective AT2R stimulation on blood pressure and renal hemodynamics in normotensive and hypertensive rats. After pretreatment with the angiotensin-converting enzyme inhibitor captopril, intravenous administration of compound 21 did not affect blood pressure and induced dose-dependent renal vasodilator responses in spontaneously hypertensive but not in normotensive rats. The D1 receptor agonist fenoldopam, used as positive control, reduced blood pressure and renal vascular resistance in both strains. The AT2R antagonist PD123319 and the nitric oxide synthase inhibitor L-NMMA (N(G)-monomethyl-L-arginine acetate) abolished the renal vasodilator response to compound 21 without affecting responses to fenoldopam. The cyclooxygenase inhibitor indomethacin partially inhibited the renal vascular response to compound 21, whereas the bradykinin B2 receptor antagonist icatibant was without effect. Angiotensin-converting enzyme inhibition unmasked a renal vasodilator response to selective AT2R stimulation in vivo, mediated by nitric oxide and partially by prostaglandins. AT2R may have a pathophysiological role to modulate renal hemodynamic effects of angiotensin II in the hypertensive state.

Association of angiotensin II type 2 receptor gene A1818T polymorphism with progression of immunoglobulin A nephropathy in Korean patients.

We determined the relationship between the progression of immunoglobulin A nephropathy (IgAN) and the A1818T polymorphism in intron 2 of Angiotensin II type 2 receptor (AT2R) gene, which might play protective roles in the pathogenesis of IgAN. Patients with biopsy-proven IgAN were recruited from the registry of the Progressive REnal disease and Medical Informatics and gEnomics Research (PREMIER) which was sponsored by the Korean Society of Nephrology. A1818T polymorphism of AT2R gene was analyzed with PCR-RFLP method and the association with the progression of IgAN, which was defined as over 50% increase in baseline serum creatinine level, was analyzed with survival analysis. Among the 480 patients followed for more than 10 months, the group without T allele had significantly higher rates of progression of IgAN than the group with T allele (11.4% vs. 3.9%, p=0.024), although there were no significant differences in the baseline variables such as initial serum creatinine level, the degree of proteinuria, and blood pressure. In the Cox's proportional hazard model, the hazard ratio of disease progression in the patients with T allele was 0.221 (95% confidence interval for Exp(B): 0.052-0.940, p=0.041) compared to that of without T allele. In conclusion, A1818T polymorphism of AT2R gene was associated with the progression of IgAN.

Association of Angiotensin II Type 2 Receptor Gene A1818T Polymorphism with Progression of Immunoglobulin A Nephropathy in Korean Patients

We determined the relationship between the progression of immunoglobulin A nephropathy (IgAN) and the A1818T polymorphism in intron 2 of Angiotensin II type 2 receptor (AT2R) gene, which might play protective roles in the pathogenesis of IgAN. Patients with biopsy-proven IgAN were recruited from the registry of the Progressive REnal disease and Medical Informatics and gEnomics Research (PREMIER) which was sponsored by the Korean Society of Nephrology. A1818T polymorphism of AT2R gene was analyzed with PCR-RFLP method and the association with the progression of IgAN, which was defined as over 50% increase in baseline serum creatinine level, was analyzed with survival analysis. Among the 480 patients followed for more than 10 months, the group without T allele had significantly higher rates of progression of IgAN than the group with T allele (11.4% vs. 3.9%, p=0.024), although there were no significant differences in the baseline variables such as initial serum creatinine level, the degree of proteinuria, and blood pressure. In the Cox's proportional hazard model, the hazard ratio of disease progression in the patients with T allele was 0.221 (95% confidence interval for Exp(B): 0.052-0.940, p=0.041) compared to that of without T allele. In conclusion, A1818T polymorphism of AT2R gene was associated with the progression of IgAN.

Changes in mRNA levels of cardiac α1-adrenergic receptor and angiotensin Ⅱ receptor subtypes with aging in rats / 中华老年医学杂志

Objective To examine the expression levels of α1-adrenergie receptor(α1-AR)and angiotensinⅡ reeeptor(ATR)subtypes in left ventricle of rats from adolescent age, middle age,presenium to senium. Methods Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) was used to quantitate the messenger RNA (mRNA) of α1-AR and ATR subtypes in left ventricle in Wistar rats aged 3-months (adolescent age), 12-months (middle age), 18-months (presenium) and 24-months (senium). Results The expression of α1A-AR mRNA was decreased gradually with aging, and the gene expression of α1 D-AR was repressed in middle age and presenium,while the expression of a,B-AR mRNA remained unchanged during senescence. Cardiac AT1R expression was not affected by aging from adolescent age to presenium, but exhibited a remarkable up-regulation in senium There was no significant discrepancies of cardiac AT2R expression among the four different age groups. Conclusions The results suggest that there are considerable changes in mRNA levels of cardiac α1-AR and ATR subtypes with aging. The change of cardiac α1-AR and ATR expression during aging is a protective response for senescence and has an important significance in maintaining normal physiological functions of heart.

Effect of angiotension Ⅱ on Apelin mRNA and APJ mRNA expression in pulmonary microvascular endothelial cells in rats / 中华麻醉学杂志

Objective To investigate the effects of angiotensinⅡ (AngⅡ) on the Apelin mRNA and APJ mRNA expression in pulmonary microvascular endothelial ceils (PMVECs) in rats. Methods Pulmonary microvascular endothelial ceils obtained from 24 h old neonatal SD rats were cultured in DMEM liquid culture medium. The 2nd-4th generation PMVECs were inoculated on 6-well plates (5×105). The experiment was performed in two parts. In part Ⅰ different concentration of AngⅡ 0, 10-9, 10-8, 10-7, 10-6mol/L (group Ⅰ- Ⅴ) were added into the PMVECs. The expression of Apelin mRNA and APJ mRNA was determined at 24 h after addition of Ang Ⅱ by RT-PCR. In part Ⅱ the cells were exposed to 10-7 mol/L Ang Ⅱ. The expression of Apelin mRNA and APJ mRNA was determined immediately and at 1, 6, 12, 24, 48 h(group Ⅰ-Ⅵ) after addition of Ang Ⅱ by RT-PCR. Results In part Ⅰ Apelin mRNA expression was significantly higher in group Ⅱ (Ang Ⅱ 10-9 mol/L) but lower in group Ⅲ-Ⅴ (AngⅡ 10-8, 10-7, 10-6 mol/L) than in group Ⅰ (control, Ang Ⅱ 0 mol/L). The APJ mRNA expression was significantly lowered in group Ⅱ-Ⅴ in a dose-dependent manner as compared with control group (group Ⅰ). In partⅡ beth Apelin mRNA and APJ mRNA expression exhibited a bi-phasic response to AngⅡ 10-7 mol/L, increased at first and was then decreasing with time. The Apelin mRNA and APJ mRNA expression reached the peak at 1 h of incubation with Ang Ⅱ respectively. Conclusion Ang Ⅱ decreases both Apelin mRNA and APJ mRNA expression in PMVECs in a dose and time dependent manner. The down-regulation of Apelin mRNA and APJ mRNA expression may be involved in the mechanism of injury to PMVECs.

Inhibition of neointimal hyperplasia after balloon angioplasty of carotid artery with transfection of adenovirus-mediated AT2R gene in rat / 解放军医学杂志

Objective To construct the recombinant adenovirus of Angiotensin Ⅱ type 2 receptor (AT2R), and study the effect of AT2R on prevention of neointimal hyperplasia in rat carotid arteries after balloon angioplasty. Methods The recombinant adenovirus of AT2R with green fluorescent protein was constructed by using the method of homogenous recombination in bacteria. AT2R gene was transduced into rat carotid arteries with pAdCMV/AT2R after the reproduction of rat carotid balloon injury restenosis model. The expression and the transfection efficiency of AT2R gene were evaluated by RT-PCR, immunofluorescence staining, and confocal microscope. The intimal/medial area ratio was measured by digital analysis system. Results The titre of purified recombinant adenovirus was 1.5?10 12pfu/ml, and it was proved by PCR. pAdCMV/AT2R transfection efficiency in carotid artery was about 40% at day14, and localized to the neointima, as well as to the media and the adventitia. pAdCMV/AT2R delivered into injured rat carotid arteries significantly up-regulated AT2RmRNA and protein expression in neointima from day 7 to 21 after injury. Compared with pAd-GFP transfection group, pAdCMV/AT2R transfection reduced I/M ratio significantly on day 21(0.78?0.06 vs. 1.36?0.21 respectively, P

Angiotensin Ⅱ AT1 receptor blockade modulates leptin,adiponectin and TNF-? in rat / 解放军医学杂志

Objective To investigate the effects of angiotensin Ⅱ AT1 receptor antagonist-Candesartan on production of leptin, adiponectin and TNF-? in rat. Methods 20 male Wistar Kyoto rats were randomly divided into vehicle and Candesartan treated groups. The dosage of Candesartan was 10mg?kg~ -1 ?d~ -1 . Food intake and bodyweight were recorded each week. Rats were sacrificed by decapitation after 17 weeks. Epididymal and perirenal fat were collected and weighted. Adipocytes were isolated from epididymal adipose tissue with collagenase. Diameter of adipocyte was evaluated. Blood chemistry, insulin, leptin, adiponectin and TNF-? were assayed. mRNA expressions of leptin, adiponectin and TNF-? of epididymal adipose tissue were assayed with RT-PCR. Results In Candesartan treated group, bodyweight and content of adipose tissue were significantly decreased, and adipocytes shrunk. Blood glucose and insulin levels showed no difference between two groups. Plasma leptin level and leptin mRNA expression in adipose tissue were lower, and plasma adiponectin level as well as adiponectin mRNA expression were higher in Candesartan treated group. Plasma TNF-? level was too low to detect with super sensitive kit, and mRNA expression of TNF? was decreased in Candesartan treated group. Conclusions Angiotensin Ⅱ AT1 receptor antagonist decreases the production of leptin and TNF-?, enhances synthesis as well as release of adiponectin in rat adipose tissue.

Role of angiotensin Ⅱ receptors in collagen synthesis of fibroblast in human hypertrophic scars / 解放军医学杂志

Objective To observe the expression of both type 1 (AT1) and type 2 (AT2) receptors of angiotensin Ⅱ (AngⅡ) in human hypertrophic scars, and to explore theirs role in collagen synthesis of fibroblasts in human hypertrophic scars. Methods The expression of both AT1 and AT2 receptors in fibroblasts of hypertrophic scars was detected with immunohistochemical staining and radioligand receptor binding assay. Collagen synthesis was examined in cultured in vitro fibroblasts of hypertrophic scars by measuring [~3H]proline incorporation into collagenous proteins. Results Positive staining signals of both AT1 and AT2 receptors were found in fibroblasts of hypertrophic scars. Similar results were also got in cultured in vitro fibroblasts of hypertrophic scars, expression level of AT1 and AT2 receptors were 10.69?2.15fmol/10~6cells and 4.9?1.05fmol/10~6cells respectively. In cultured in vitro fibroblasts, AngⅡ may accelerate the collagen synthesis significantly (P