Current knowledge on the renin-angiotensin system (RAS) indicates its central role in the pathogenesis of cardiovascular remodelling via both hemodynamic alterations and direct growth and the proliferation effects of angiotensin II or aldosterone resulting in the hypertrophy of cardiomyocytes, the proliferation of fibroblasts, and inflammatory immune cell activation. The noncoding regulatory microRNAs has recently emerged as a completely novel approach to the study of the RAS. A growing number of microRNAs serve as mediators and/or regulators of RAS-induced cardiac remodelling by directly targeting RAS enzymes, receptors, signalling molecules, or inhibitors of signalling pathways. Specifically, microRNAs that directly modulate pro-hypertrophic, pro-fibrotic and pro-inflammatory signalling initiated by angiotensin II receptor type 1 (AT1R) stimulation are of particular relevance in mediating the cardiovascular effects of the RAS. The aim of this review is to summarize the current knowledge in the field that is still in the early stage of preclinical investigation with occasionally conflicting reports. Understanding the big picture of microRNAs not only aids in the improved understanding of cardiac response to injury but also leads to better therapeutic strategies utilizing microRNAs as biomarkers, therapeutic agents and pharmacological targets.

• Keywords
• RAS, cardiac fibrosis, cardiac hypertrophy, cardiac remodelling, miRNA,
• MeSH
• Fibrosis MeSH
• Cardiomegaly genetics   metabolism   pathology   MeSH
• Humans MeSH
• MicroRNAs genetics   metabolism   MeSH
• Myocardium metabolism   pathology   MeSH
• Heart Diseases genetics   metabolism   pathology   MeSH
• Renin-Angiotensin System * MeSH
• Signal Transduction * MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• MicroRNAs MeSH

The renin-angiotensin-aldosterone system (RAAS) ranks among the most challenging puzzles in cardiovascular medicine [...].

• MeSH
• COVID-19 physiopathology   therapy   MeSH
• Humans MeSH
• Renin-Angiotensin System * MeSH
• SARS-CoV-2 metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Editorial MeSH

The renin-angiotensin-aldosterone system (RAAS) is a dominant player in several cardiovascular pathologies. This study investigated whether alterations induced by l-NAME, (NLG)-nitro-l-arginine methyl ester, a nitric oxide synthase inhibitor, and the protective effect of melatonin are associated with changes in the RAAS. Four groups of 3-month-old male Wistar rats (n = 10) were treated as follows for four weeks: untreated controls, rats treated with melatonin (10 mg/kg/day), rats treated with l-NAME (40 mg/kg/day), and rats treated with l-NAME + melatonin. l-NAME administration led to hypertension and left ventricular (LV) fibrosis in terms of enhancement of soluble, insoluble and total collagen concentration and content. Melatonin reduced systolic blood pressure enhancement and lowered the concentration and content of insoluble and total collagen in the LV. The serum concentration of angiotensin (Ang) 1-8 (Ang II) and its downstream metabolites were reduced in the l-NAME group and remained unaltered by melatonin. The serum aldosterone level and its ratio to Ang II (AA2-ratio) were increased in the l-NAME group without being modified by melatonin. We conclude that l-NAME-hypertension is associated with reduced level of Ang II and its downstream metabolites and increased aldosterone concentration and AA2-ratio. Melatonin exerts its protective effect in l-NAME-induced hypertension without affecting RAAS.

• Keywords
• ">l-NAME, aldosterone, angiotensin 1–7, angiotensin II, fibrosis, melatonin,
• MeSH
• Hypertension * chemically induced   metabolism   physiopathology   prevention & control   MeSH
• Blood Pressure drug effects   MeSH
• Rats MeSH
• Melatonin pharmacology   MeSH
• NG-Nitroarginine Methyl Ester adverse effects   pharmacology   MeSH
• Rats, Wistar MeSH
• Renin-Angiotensin System drug effects   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Melatonin MeSH
• NG-Nitroarginine Methyl Ester MeSH

Lactacystin is a proteasome inhibitor that interferes with several factors involved in heart remodelling. The aim of this study was to investigate whether the chronic administration of lactacystin induces hypertension and heart remodelling and whether these changes can be modified by captopril or melatonin. In addition, the lactacystin-model was compared with NG-nitro-l-arginine-methyl ester (L-NAME)- and continuous light-induced hypertension. Six groups of three-month-old male Wistar rats (11 per group) were treated for six weeks as follows: control (vehicle), L-NAME (40 mg/kg/day), continuous light (24 h/day), lactacystin (5 mg/kg/day) alone, and lactacystin with captopril (100 mg/kg/day), or melatonin (10 mg/kg/day). Lactacystin treatment increased systolic blood pressure (SBP) and induced fibrosis of the left ventricle (LV), as observed in L-NAME-hypertension and continuous light-hypertension. LV weight and the cross-sectional area of the aorta were increased only in L-NAME-induced hypertension. The level of oxidative load was preserved or reduced in all three models of hypertension. Nitric oxide synthase (NOS) activity in the LV and kidney was unchanged in the lactacystin group. Nuclear factor-kappa B (NF-κB) protein expression in the LV was increased in all treated groups in the cytoplasm, however, in neither group in the nucleus. Although melatonin had no effect on SBP, only this indolamine (but not captopril) reduced the concentration of insoluble and total collagen in the LV and stimulated the NO-pathway in the lactacystin group. We conclude that chronic administration of lactacystin represents a novel model of hypertension with collagenous rebuilding of the LV, convenient for testing antihypertensive drugs or agents exerting a cardiovascular benefit beyond blood pressure reduction.

• Keywords
• captopril, fibrosis, hypertension, lactacystin, melatonin, remodelling,
• MeSH
• Acetylcysteine adverse effects   analogs & derivatives   MeSH
• Antihypertensive Agents administration & dosage   pharmacology   MeSH
• Fibrosis MeSH
• Hypertension chemically induced   drug therapy   etiology   MeSH
• Captopril administration & dosage   pharmacology   MeSH
• Rats MeSH
• Melatonin administration & dosage   pharmacology   MeSH
• Disease Models, Animal MeSH
• NG-Nitroarginine Methyl Ester adverse effects   MeSH
• Rats, Wistar MeSH
• Ventricular Remodeling drug effects   MeSH
• Heart Ventricles drug effects   pathology   MeSH
• Light adverse effects   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH
• Names of Substances
• Acetylcysteine MeSH
• Antihypertensive Agents MeSH
• Captopril MeSH
• lactacystin MeSH Browser
• Melatonin MeSH
• NG-Nitroarginine Methyl Ester MeSH