Mineralocorticoid Receptor and Aldosterone-Related Biomarkers of End-Organ Damage in Cardiometabolic Disease

Abstract

The mineralocorticoid receptor (MR) was first identified as a blood pressure regulator, modulating renal sodium handling in response to its principal ligand aldosterone. The mineralocorticoid receptor is also expressed in many tissues other than the kidney, such as adipose tissue, heart and vasculature. Recent studies have shown that MR plays a relevant role in the control of cardiovascular and metabolic function, as well as in adipogenesis. Dysregulation of aldosterone/MR signaling represents an important cause of disease as high plasma levels of aldosterone are associated with hypertension, obesity and increased cardiovascular risk. Aldosterone displays powerful vascular effects and acts as a potent pro-fibrotic agent in cardiovascular remodeling. Mineralocorticoid receptor activation regulates genes involved in vascular and cardiac fibrosis, calcification and inflammation. This review focuses on the role of novel potential biomarkers related to aldosterone/MR system that could help identify cardiovascular and metabolic detrimental conditions, as a result of altered MR activation. Specifically, we discuss: (1) how MR signaling regulates the number and function of different subpopulations of circulating and intra-tissue immune cells; (2) the role of aldosterone/MR system in mediating cardiometabolic diseases induced by obesity; and (3) the role of several MR downstream molecules as novel potential biomarkers of cardiometabolic diseases, end-organ damage and rehabilitation outcome.

The neuropeptide substance P regulates aldosterone secretion in human adrenals

“…NK1R antagonists like aprepitant may thus represent a valuable therapeutic option to reduce obesity-and SAS-associated hyperaldosteronism, manage low renin hypertension and limit aldosterone breakthrough. In fact, it is now well demonstrated that aldosterone exerts profibrotic and inflammation actions in the cardiovascular system and kidney, and counteracting its effects has proved its efficacy to reduce the progression of heart failure and chronic nephropathy 36,37 . Especially, NK1R antagonists may constitute an alternative to both mineralocorticoid receptor antagonists whose utilisation is hampered by their antiandrogenic properties 38,39 , and aldosterone synthase inhibitors whose administration leads to accumulation of steroid precursors with mineralocorticoid activity 40 , a phenomenon which may reduce their clinical benefits.…”

Aldosterone Contributed to Pulmonary Arterial Hypertension Development via Stimulating Aquaporin Expression and Pulmonary Arterial Smooth Muscle Cells Proliferation

“…The RAAS plays a very important role in regulating cardiovascular function, but it may also lead to the occurrence and development of various cardiovascular diseases, including cardiac hypertrophy and heart failure [33,34]. More and more evidence has shown that ALDO plays an important role in the pathological development of cardiovascular disease [33][34][35]. Calvier et al [36] proved that in PAH, ALDO was considered to be a potential tandem biomarker.…”

The role of aldosterone in the development of atrial fibrillation: modern understanding of problem

“…В последние годы получены неоспоримые доказательства, что спектр действия альдостерона лежит далеко за пределами узкого перечня «почечных» эффектов. Системная или локальная гиперпродукция гормона вызывает целый ряд патологических реакций [19][20][21][22][23][24]…”