A5061044642- Hormonal Regulation and Hypertension
- Estrogen and related hormone effects
- Adrenal and Paraganglionic Tumors
- Adrenal Hormones and Disorders
- Ion Transport and Channel Regulation
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Nitric Oxide and Endothelin Effects
- Angiogenesis and VEGF in Cancer
- Electrolyte and hormonal disorders
- Renin-Angiotensin System Studies
- Cancer, Hypoxia, and Metabolism
- Receptor Mechanisms and Signaling
- MicroRNA in disease regulation
- Sirtuins and Resveratrol in Medicine
- Adipokines, Inflammation, and Metabolic Diseases
- Apelin-related biomedical research
- Heat shock proteins research
- Circular RNAs in diseases
- Adipose Tissue and Metabolism
- Blood Pressure and Hypertension Studies
- Antioxidant Activity and Oxidative Stress
- Menopause: Health Impacts and Treatments
- Autophagy in Disease and Therapy
- Ion channel regulation and function
University of Mississippi Medical Center
2014-2018
University of Mississippi
2015-2017
G.V. (Sonny) Montgomery VA Medical Center
2017
Jackson Memorial Hospital
2017
University of Padua
2012-2015
Anna University, Chennai
2010-2013
Atherosclerosis is an inflammatory disease wherein cholesterol-loaded macrophages play a major role. MicroRNAs and microparticles propagate pathways are involved in cardiovascular disease. We aimed to screen validate circulating microRNAs correlated with atherosclerosis development humans, dissect the molecular mechanisms associated atherogenesis using vitro vivo approaches.A panel of 179 secreted was screened plasma samples patients without atherosclerosis, validated cross-sectionally...
Abstract Fertile women have lower blood pressure and cardiovascular risk than age-matched men, which suggests that estrogens exert protective effects. However, whether 17 β-estradiol (E2) blunts aldosterone secretion, thereby affects the gender dimorphism of pressure, is unknown. We therefore sought for estrogen receptor (ER) subtypes in human adrenocortical tissues ex vivo by performing gene protein expression studies. also investigated effect E2 on synthesis involved receptors through...
Understanding the function of KCNJ5 potassium channel through characterization naturally occurring novel mutations is key for dissecting mechanism(s) autonomous aldosterone secretion in primary aldosteronism.We sought such a large database patients with aldosterone-producing adenomas (APAs).We discovered somatic c.446insAAC insertion, resulting mutant protein KCNJ5-insT149, patient severe drug-resistant hypertension among 195 consecutive conclusive diagnosis APA, 24.6% whom showed mutations....
The molecular mechanisms of primary aldosteronism, a common cause human hypertension, are unknown, but alterations K(+) channels can play key role.The objective the study was to investigate following: 1) expression Twik-related acid-sensitive (TASK) in aldosterone producing adenomas (APAs); 2) role TASK-2 synthesis; and 3) determinants TASK-2-blunted APAs.We analyzed transcriptome microRNA profiles 32 consecutive APAs investigated protein localization APA adrenocortical cell lines (H295R...
Objective: Aldosterone exerts detrimental cardiovascular effects, and patients with an aldosterone-producing adenoma (APA) carrying somatic mutations in the KCNJ5 K+ channel (mutAPA) have higher plasma aldosterone concentration than wild-type APA (wtAPA) patients. We therefore investigated whether mutAPA develop a more prominent damage wtAPA Methods findings: From 257 consecutive primary aldosteronism patients, we identified 176 who had both diagnosis of by 'four corners' criteria...
Somatic mutations in the selectivity filter of KCNJ5 K(+) channel were found to be associated with higher plasma aldosterone concentrations patients an aldosterone-producing adenoma (APA).We investigated whether levels and lateralization index are from side APA mutation, as compared those without mutation.From 170 consecutive comprehensive clinical data a conclusive diagnosis, we recruited 91 adrenal vein sampling follow-up data. We measured CYP11B1 CYP11B2 mRNA tissue (PAC) cortisol (PCC)...
The mineralocorticoid receptor (MR) is a member of the steroid-thyroid hormone superfamily ligand-dependent transcription factors with diverse functions including biological actions aldosterone. Identification various transcriptional coregulators MR essential for understanding complexity signaling pathways under physiological and pathological conditions. We used yeast two-hybrid system to find proteins that interact full-length found, among other proteins, interacted specifically activated C...
Because blunted expression of the twik-related acid-sensitive K+ channel 2 (TASK-2) is a common feature aldosterone-producing adenoma (APA) causing primary aldosteronism (PA), we sequenced promoter region TASK-2 gene (KCNK5) in APAs (n = 76), hypertensive patients 98), and 20-year-old healthy volunteers 71), searching for variants that could affect this channel. We found mutations 25% APAs: C999T 6.6%, G595A 5.3%, G36A C562T, Gins468, G265C, C1247T, G1140T, C1399T 1.3% each. The mutation was...
Introduction: Hypertension and diabetes are independent risk factors for cardiovascular disease, however why they frequently occur together is not clear. Inappropriate mineralocorticoid receptor (MR) activation associated with the metabolic syndrome, as well hypertension abnormal remodeling. MR antagonists effective in reducing delaying onset of renal complications despite circulating aldosterone levels that within normal limits. Glucose concentrations increase O-glycosylation many proteins,...
The mineralocorticoid receptor (MR) is a multifunctional ligand dependent transcription factor in the steroid superfamily. MR mediates aldosterone regulation of electrolytes and blood pressure. transcriptional co-regulators to influence specific gene transcription. We used yeast two-hybrid system find proteins that interact with full-length as bait. Results: Among other proteins, we found interaction RACK1 (Receptor for Activated C Kinase 1), scaffolding protein. Overexpression using...
Although adult females are protected, the cerebrovascular disease is greater in aged post-menopause than age matched males, but role of vascular function and large conductance potassium (BK) channel not clear. We hypothesize that “compared to cerebral vasculature intact female rats displays an attenuated myogenic response intrinsic tone due differential expression BK subunits. Aging or menopause exaggerates response, diminishes thus, vasodilatory capacity more males a reduction subunit...
Visinin-Like Protein-1(Vsnl1) is a member of the EF-hand calcium sensor proteins. Its mRNA was found to be upregulated in aldosterone-producing adenomas and expressed zona glomerulosa (ZG) rat human adrenal. We studied expression pattern Vsnl1 its co-localization with CYP11B2 enzyme ZG marker Dlk1 (ZOG) using double triple immunofluorescence adrenal glands rats on normal, high low sodium diets effect mobilization aldosterone biosynthesis adrenocarcinoma cell line, HAC15 cell. In adrenals,...
Context: Understanding the function of Kir3.4 (KCNJ5 gene) potassium channel through characterization occurring novel mutations is key for dissecting mechanism(s) autonomous aldosterone secretion in primary aldosteronism. Objective: To identify KCNJ5 and functionally characterize them a large database patients with aldosterone-producing adenomas (APA). Methods: We sequenced APA germinal DNA 195 consecutive patients, diagnosed four corners criteria PAPY study. Among 24.6% (48/195) who showed...
Objective: We previously showed that a blunted expression of the Twik-related Acid-Sensitive K+ channel 2 (TASK-2) is common feature Aldosterone Producing Adenoma (APA). Thus, we aimed at investigating presence mutations in promoter region TASK-2 gene (KCNK5) APA. Design and method: sequenced entire 88 APA 98 primary hypertensive patients (controls). next tested vitro effects most frequently detected mutation by fusing mutated wild type to luciferase coding sequence transfecting reporter...
Aldosterone exerts detrimental cardiovascular (CV) effects, and aldosterone producing adenoma (APA) patients carrying somatic mutations in the KCNJ5 K+ channel (mutAPA) have higher plasma concentration (PAC) than those wild-type (wtAPA). We therefore investigated whether mutAPA develop a more prominent CV renal damage wtAPA patients. From 250 consecutive PA patients, we identified 170 who had diagnosis of APA by 'four corners' criteria high-quality echocardiographic data. Of them 106 with...
Background. Fertile women have lower blood pressure and are held to be at risk for cardiovascular events than age-matched man. However, whether this gender dimorphism involves a modulation of aldosterone synthesis by 17 beta-estradiol (E2) is unknown. Aims. i) To investigate estrogen receptor subtypes gene expression in the normal human adrenal cortex (NAC), producing adenoma (APA) adrenocortical carcinoma cell line (HAC15); ii) assess effect E2 on synthase (CYP11B2) identify involved...