Role of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension

Muñoz‐Durango, Natalia; Fuentes, César M.; Castillo, Andrés; González-Gómez, Luis M; Vecchiola, Andrea; Fardella, Carlos E.; Kalergis, Alexis M.

doi:10.3390/ijms17070797

Cited by 218 publications

(167 citation statements)

References 131 publications

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“…Renin-angiotensin system (RAS) plays a critical role in the development of hypertension and the end-organ damage in hypertension [5]. Ang II is a powerful vasoconstrictor and contributes to hypertension [6].…”

Section: Introductionmentioning

confidence: 99%

NLRP3 Gene Deletion Attenuates Angiotensin II-Induced Phenotypic Transformation of Vascular Smooth Muscle Cells and Vascular Remodeling

Ren

Tong

et al. 2017

Cell Physiol Biochem

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Background/Aims: Angiotensin (Ang) II plays vital roles in vascular inflammation and remodeling in hypertension. Phenotypic transformation of vascular smooth muscle cells (VSMCs) is a major initiating factor for vascular remodeling. The present study was designed to determine the roles of NLRP3 inflammasome activation in Ang II-induced VSMC phenotypic transformation and vascular remodeling in hypertension. Methods: Primary VSMCs from the aorta of NLRP3 knockout (NLRP3^-/-) mice and wild-type (WT) mice were treated with Ang II for 24 h. Subcutaneous infusion of Ang II via osmotic minipump for 2 weeks was used to induce vascular remodeling and hypertension in WT and NLRP3^-/- mice. Results: NLRP3 gene deletion attenuates Ang II-induced NLRP3 inflammasome activation, phenotypic transformation from a contractile phenotype to a synthetic phenotype and proliferation in primary mice VSMCs. Ang II-induced hypertension and vascular remodeling in WT mice were attenuated in NLRP3^-/- mice. Furthermore, Ang II-induced NLRP3 inflammasome activation, phenotypic transformation and proliferating cell nuclear antigen (PCNA) upregulation were inhibited in the media of aorta of NLRP3^-/- mice. Conclusions: NLRP3 inflammasome activation contributes to Ang II-induced VSMC phenotypic transformation and proliferation as well as vascular remodeling and hypertension.

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Section: Introductionmentioning

confidence: 99%

NLRP3 Gene Deletion Attenuates Angiotensin II-Induced Phenotypic Transformation of Vascular Smooth Muscle Cells and Vascular Remodeling

Ren

Tong

et al. 2017

Cell Physiol Biochem

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“…Then, Ang I is hydrolyzed to Ang II-IX by angiotensin-converting enzymes (ACE). Ang II is a biological key hormone, and its function is mediated through the receptors of Ang II type 1 (AGTR1) or Ang II type 2 (AGTR2) [21]. Excessive activation of AGTR1 results in increased expression levels of the extracellular matrix components, such as collagen 1 (COL1) and collagen 3 (COL3) [22], which are distributed in several layers of the heart wall to provide rigidity and elasticity [23].…”

Section: Introductionmentioning

confidence: 99%

Alteration in the expression of the renin-angiotensin system in the myocardium of mice conceived by in vitro fertilization†

Wang

Zhang

Fang

et al. 2018

Biology of Reproduction

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Epidemiological studies have revealed that offspring conceived by in vitro fertilization (IVF) have an elevated risk of cardiovascular malformations at birth, and are more predisposed to cardiovascular diseases. The renin-angiotensin system (RAS) plays an essential role in both the pathogenesis of congenital heart disease in fetuses and cardiovascular dysfunction in adults. This study aimed to assess the relative expression levels of genes in the RAS pathway in mice conceived using IVF, compared to natural mating with superovulation. Results demonstrated that expression of the angiotensin II receptor type 1 (AGTR1), connective tissue growth factor (CTGF), and collagen 3 (COL3), in the myocardial tissue of IVF-conceived mice, was elevated at 3 weeks, 10 weeks, and 1.5 years of age, when compared to their non-IVF counterparts. These data were supported by microRNA microarray analysis of the myocardial tissue of aged IVF-conceived mice, where miR-100, miR-297, and miR-758, which interact with COL3, AGTR1, and COL1 respectively, were upregulated when compared to naturally mated mice of the same age. Interestingly, bisulfite sequencing data indicated that IVF-conceived mice exhibited decreased methylation of CpG sites in Col1. In support of our in vivo investigations, miR-297 overexpression was shown to upregulate AGTR1 and CTGF, Effects of in vitro fertilization on myocardium, 2018, Vol. 99, No. 6 1277 and increased cell proliferation in cultured H9c2 cardiomyocytes. These findings indicate that the altered expression of RAS in myocardial tissue might contribute to cardiovascular malformation and/or dysfunction in IVF-conceived offspring. Furthermore, these cardiovascular abnormalities might be the result of altered DNA methylation and abnormal regulation of microRNAs. Summary SentenceAltered expression of the renin-angiotensin system in myocardial tissue might contribute to an increased risk of cardiovascular malformations and dysfunction in IVF offspring, and is involved in abnormal regulations of DNA methylation and microRNAs.

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“…Chronic inlammation directly stimulates RAAS, which causes HTN [37]. Since frail patients have persistently increased inlammation, stimulating RAAS, they are more likely to develop HTN.…”

Section: Frailty and Hypertension (Htn)mentioning

confidence: 99%

Frailty and Cardiovascular Disease

Chainani¹,

Riehl²,

Chainani³

et al. 2017

Frailty and Sarcopenia - Onset, Development and Clinical Challenges

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Cardiovascular disease (CVD) comprises a vast spectrum of disease states ranging from hypertension (HTN) to valvular heart disease (VHD). CVD is known to be the leading cause of morbidity, mortality, and health-care expenditure throughout the world. According to the World Health Organization, coronary artery disease (CAD) and stroke, both subsets of CVD, are the world's biggest killers, accounting for a combined 15 million deaths in 2015. These diseases have remained the leading causes of death globally in the last 15 years. In 2010, CAD alone was projected to cost the U.S. $108.9 billion including the cost of health-care services, medications, and lost productivity. The presence of frailty signiicantly worsens outcomes for patients sufering from CAD. With just this one example of how frailty afects CVD, it is clear that understanding the impact of frailty upon patients alicted with the spectrum of cardiovascular disease is integral for the care of this very signiicant patient population.

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Role of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension

Cited by 218 publications

References 131 publications

NLRP3 Gene Deletion Attenuates Angiotensin II-Induced Phenotypic Transformation of Vascular Smooth Muscle Cells and Vascular Remodeling

NLRP3 Gene Deletion Attenuates Angiotensin II-Induced Phenotypic Transformation of Vascular Smooth Muscle Cells and Vascular Remodeling

Alteration in the expression of the renin-angiotensin system in the myocardium of mice conceived by in vitro fertilization†

Frailty and Cardiovascular Disease

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