Primary Aldosteronism

Background and Objective:Primary aldosteronism (PA) is characterized by the overproduction of the mineralocorticoid hormone aldosterone by the adrenal glands. Such inappropriately high production of aldosterone causes suppression of plasma renin, sodium retention, hypertension, cardiovascular damage, and potassium excretion that if prolonged and severe may lead to hypokalemia. Elevated plasma aldosterone level is one of its characteristics. It mediates a variety of pathological processes, and plays a key role in PA complications such as cardiovascular diseases, nephropathy and metabolism abnormal. This research was carried out from two aspects:clinical analyses and basic research.Part1:To investigate the prevalence of PA in resistant hypertension, and analyze the clinical characteristics and related factors of PA.Part2:To investigate the effects of aldosterone on the human umbilical vein endothelial cells (HUVECs) proliferation, migration and senescence, find out the expressive difference of miRNA under this aldosterone treatment, and investigate the effects and mechanisms of miR-34a on aldosterone-induced endothelial senescence. Methods:Part1:Between January2010and August2013, a multicenter epidemiologic study was conducted among111patients with resistant hypertension from3hospital in Hangzhou. Meanwhile, combined with PA patients from the department of endocrinology, cardiovascular and urology, the analyses of clinical characteristics and related factors in patients with PA were performed to investigate the differences among PA, low renin essential hypertension and normal or high renin essential hypertension.Part2:HUVECs were cultured in vitro with1640medium plus10%fetal bovine serum. Cells were incubated with aldosterone. Then, the proliferation ability of HUVECs was detected by using MTS test. Wound healing test was used for detecting the mobility of HUVECs. SA-β-gal staining assay as well as TRAP-ELISA assay (telomeric repeat amplification protocol-enzyme linked immunosorbent assay) were used for measuring the cell senescence. Through the literature search,8vascular endothelial function related miRNAs (miR-21, miR-19a, miR-17-5p, miR-126, miR-320a; miR-31, miR-34a, miR-130a) were selected and the expression levels of these miRs were evaluated by qRT-PCR. Further, using miR-34a inhibitor, we downregulate the level of miR-34a in HUVECs. Then MTS test, SA-β-gal staining assay and TRAP-ELISA assay were used as above.Results:Part1:The prevalence rate of PA in resistant hypertension was7.2%. Compared with low renin essential hypertensives and normal or high renin essential hypertensives, patients with PA had short hypertension duration, and body mass index, diastolic blood pressure, serum albumin, serum creatinine, serum potassium, blood calcium and fasting plasma glucose were all lower. In addition, the prevalence of metabolic disorder syndrome in PA was also lower. Analysis of regression found that body mass index and serum potassium were independently associated with PA.Part2:Aldosterone treatment could inhibit the proliferation and migration of HUVECs. And endothelial cells exhibited the characteristic of senescence, e.g., they increased in size, displayed a more flat morphology and increased the number of β-gal positive cells. Furthermore, the telomerase activity was decreased. qRT-PCR array showed that the level of miR-34a was significantly upregulated by aldosterone(10nmol/L,48hours). Downregulation of miR-34a by its inhibitor totally abolished the effects of aldosterone on HUVECs cell senescence.Conclusion:Part1:The prevalence of PA in resistant hypertension was accounted for7.2%. Compared with resistant essential hypertensives, patients with PA had less metabolic syndrome factors; body mass index and serum potassium were independently associated with PA.Part2:Aldosterone inhibits HUVEC proliferation and migration as well as promotes cell senescence. And aldosterone significantly upregulated the level of miR-34a. Downregulation of miR-34a reverse the effects of aldosterone on HUVECs cell senescence. So miR-34a may play an important role in aldosterone-induced cell senescence.