Role of the Renin-Angiotensin System in Cardiovascular Disease

Cohn, Jay N.

doi:10.1007/s10557-010-6230-3

Cited by 26 publications

(21 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The renin-angiotensin-aldosterone system (RAAS), a neurohormonal system, plays a central role in the progression of heart failure (HF) [5,6]. The continued activation of the RAAS may be instrumental in the further development and progression of HF related to increasing morbidity and mortality [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

The predictability of renin–angiotensin–aldosterone system factors for clinical outcome in patients with acute decompensated heart failure

et al. 2015

View full text Add to dashboard Cite

Although counter-regulation between B-type natriuretic peptide (BNP) levels and renin-angiotensin-aldosterone system (RAAS) activation in heart failure (HF) has been suggested, whether the regulation is preserved in acute decompensated heart failure (ADHF) patients remains unclear. This study aimed to determine: (1) the relationship between RAAS activation and clinical outcomes in ADHF patients, and (2) the relationships between plasma BNP levels and degrees of activation in RAAS factors. This study included ADHF patients (n = 103, NYHA3-4, plasma BNP > 200 pg/ml). We studied the predictability of RAAS factors for cardiovascular events and the relationships between plasma BNP levels and the degrees of activation in RAAS factors, which were evaluated by plasma renin activity (PRA) and aldosterone concentration (PAC). PRA was a strong predictor of cardiovascular (CV) events over 1 year, even after accounting for plasma BNP levels (hazard ratio (HR): 1.04, CI [1.02-1.06], p < 0.01) and medication such as RAAS blockers (HR: 1.03, CI [1.01-1.05], p < 0.01), whereas PAC was borderline-significant (univariate analysis, p = 0.06). Cut-off value of PRA (5.3 ng/ml/h) was determined by AUC curve. Of the enrolled patients, higher PRA was found in 40 % of them. Although no correlation between the plasma BNP levels and PRA was found (p = 0.36), after adjusting for hemodynamic parameters, eGFR and medication, a correlation was found between them (p = 0.01). Elevated RAAS factors were found in a substantial number of ADHF patients with high plasma BNP levels in the association with hemodynamic state, which predicts poor clinical outcomes. The measurements of RAAS factors help to stratify ADHF patients at risk for further CV events.

show abstract

Section: Introductionmentioning

confidence: 99%

The predictability of renin–angiotensin–aldosterone system factors for clinical outcome in patients with acute decompensated heart failure

et al. 2015

View full text Add to dashboard Cite

show abstract

“…ANG II also regulates cell proliferation and angiogenesis (12,22). Pathological activation of the RAS is associated with cardiovascular diseases, including hypertension and heart failure, and is consequently a major target of therapeutic agents (11).…”

mentioning

confidence: 99%

Renin expression in developing zebrafish is associated with angiogenesis and requires the Notch pathway and endothelium

Rider

Mullins

Verdon

et al. 2015

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

Rider SA, Mullins LJ, Verdon RF, MacRae CA, Mullins JJ. Renin expression in developing zebrafish is associated with angiogenesis and requires the Notch pathway and endothelium. Am J Physiol Renal Physiol 309: F531-F539, 2015. First published July 22, 2015 doi:10.1152/ajprenal.00247.2015.-Although renin is a critical regulatory enzyme of the cardiovascular system, its roles in organogenesis and the establishment of cardiovascular homeostasis remain unclear. Mammalian renin-expressing cells are widespread in embryonic kidneys but are highly restricted, specialized endocrine cells in adults. With a functional pronephros, embryonic zebrafish are ideal for delineating the developmental functions of renin-expressing cells and the mechanisms governing renin transcription. Larval zebrafish renin expression originates in the mural cells of the juxtaglomerular anterior mesenteric artery and subsequently at extrarenal sites. The role of renin was determined by assessing responses to renin-angiotensin system blockade, salinity variation, and renal perfusion ablation. Renin expression did not respond to renal flow ablation but was modulated by inhibition of angiotensin-converting enzyme and altered salinity. Our data in larval fish are consistent with conservation of renin's physiological functions. Using transgenic renin reporter fish, with mindbomb and cloche mutants, we show that Notch signaling and the endothelium are essential for developmental renin expression. After inhibition of angiogenesis, renin-expressing cells precede angiogenic sprouts. Arising from separate lineages, but relying on mutual interplay with endothelial cells, renin-expressing cells are among the earliest mural cells observed in larval fish, performing both endocrine and paracrine functions. renin; zebrafish; notch; endothelium; angiogenesis RENIN is the rate-limiting enzyme of the renin-angiotensin system (RAS). Mammalian ANG II, the effector of the RAS, is principally involved in blood pressure homeostasis by regulation of vasomotor tone and Na ϩ retention. ANG II also regulates cell proliferation and angiogenesis (12,22). Pathological activation of the RAS is associated with cardiovascular diseases, including hypertension and heart failure, and is consequently a major target of therapeutic agents (11).Renin and its cognate cells are required for normal renal development (2), including angiogenesis of the renal vascular tree (59). In mice, ablation of the renin gene or renin-expressing cells leads to renal developmental abnormalities (55,71,79). The vasculature of mammalian embryonic kidneys have a transient but extensive coverage of mural renin-expressing cells (17,31,32,47,63); however, their function is unclear. Adult renin-expressing cells are restricted to the juxtaglomerular apparatus and play a vital role in ion homeostasis by secreting activated renin enzyme via cytoplasmic granules (17,31,36,63). Upon physiological challenge by RAS inhibition or low Na ϩ , prearteriolar vascular smooth muscle cells (VSMC) reestablish their embryonic re...

show abstract

“…Both brain natriuretic peptide (BNP) and the N-terminal fragment of pro-BNP are well-estab- lished biomarkers used for the diagnosis of heart failure [16] and their utility as risk markers in CAD have been investigated extensively [17][18][19][20][21]. Renin is part of the renin-angiotensin-aldosterone system and might contribute to the development and progression of cardiovascular disease [22]. Renin has been associated with mortality in the Framingham Offspring Study whereas no association with cardiovascular events was found [23,24].…”

Section: Discussionmentioning

confidence: 99%

Evolving biomarkers improve prediction of long‐term mortality in patients with stable coronary artery disease: the BIO‐VILCAD score

et al. 2014

View full text Add to dashboard Cite

Objective Algorithms to predict the future long‐term risk of patients with stable coronary artery disease (CAD) are rare. The VIenna and Ludwigshafen CAD (VILCAD) risk score was one of the first scores specifically tailored for this clinically important patient population. The aim of this study was to refine risk prediction in stable CAD creating a new prediction model encompassing various pathophysiological pathways. Therefore, we assessed the predictive power of 135 novel biomarkers for long‐term mortality in patients with stable CAD. Design, setting and subjects We included 1275 patients with stable CAD from the LUdwigshafen RIsk and Cardiovascular health study with a median follow‐up of 9.8 years to investigate whether the predictive power of the VILCAD score could be improved by the addition of novel biomarkers. Additional biomarkers were selected in a bootstrapping procedure based on Cox regression to determine the most informative predictors of mortality. Results The final multivariable model encompassed nine clinical and biochemical markers: age, sex, left ventricular ejection fraction (LVEF), heart rate, N‐terminal pro‐brain natriuretic peptide, cystatin C, renin, 25OH‐vitamin D3 and haemoglobin A1c. The extended VILCAD biomarker score achieved a significantly improved C‐statistic (0.78 vs. 0.73; P = 0.035) and net reclassification index (14.9%; P < 0.001) compared to the original VILCAD score. Omitting LVEF, which might not be readily measureable in clinical practice, slightly reduced the accuracy of the new BIO‐VILCAD score but still significantly improved risk classification (net reclassification improvement 12.5%; P < 0.001). Conclusion The VILCAD biomarker score based on routine parameters complemented by novel biomarkers outperforms previous risk algorithms and allows more accurate classification of patients with stable CAD, enabling physicians to choose more personalized treatment regimens for their patients.

show abstract

Role of the Renin-Angiotensin System in Cardiovascular Disease

Cited by 26 publications

References 35 publications

The predictability of renin–angiotensin–aldosterone system factors for clinical outcome in patients with acute decompensated heart failure

The predictability of renin–angiotensin–aldosterone system factors for clinical outcome in patients with acute decompensated heart failure

Renin expression in developing zebrafish is associated with angiogenesis and requires the Notch pathway and endothelium

Evolving biomarkers improve prediction of long‐term mortality in patients with stable coronary artery disease: the BIO‐VILCAD score

Contact Info

Product

Resources

About