Relation of Plasma Renin Activity to Subclinical Peripheral and Coronary Artery Disease (from the Multiethnic Study of Atherosclerosis)

Manca

Front. Cardiovasc. Med.

et al. 2022

BackgroundProteomics of atypical phenotypes may help unravel cardiovascular disease mechanisms.AimWe aimed to prospectively screen the proteome of four types of individuals: with or without coronary artery disease (CAD), each with or without multiple risk factors. Associations with individual risk factors and circulating biomarkers were also tested to provide a functional context to the protein hits.Materials and MethodsThe CAPIRE study (ClinicalTrials.gov Identifier: NCT02157662) is a cross-sectional study aimed at identifying possible new mechanisms promoting or protecting against atherothrombosis. Quantification (by aptamer technology), ranking (using partial least squares), and correlations (by multivariate regression) of ~5000 plasma proteins were performed in consecutive individuals aged 45–75 years, without previous cardiovascular disease, undergoing computed tomography angiography for suspected CAD, showing either >5/16 atherosclerotic segments (CAD+) or completely clean arteries (CAD−) and either ≤ 1 risk factor (RF+) or ≥3 risk factors (RF−) (based on history, blood pressure, glycemia, lipids, and smoking).ResultsOf 544 individuals, 39% were atypical (93 CAD+/RF−; 120 CAD−/RF+) and 61% typical (102 CAD+/RF+; 229 CAD−/RF−). In the comparison with CAD+/RF− adjusted for sex and age, CAD−/RF+ was associated with increased atrial myosin regulatory light chain 2 (MYO) and C-C motif chemokine-22 (C-C-22), and reduced protein shisa-3 homolog (PS-3) and platelet-activating factor acetylhydrolase (PAF-AH). Extending the analysis to the entire cohort, an additional 8 proteins were independently associated with CAD or RF; by logistic regression, the 12-protein panel alone discriminated the four groups with AUCROC's of 0.72–0.81 (overall p = 1.0e−38). Among them, insulin-like growth factor binding protein-3 is positively associated with RF, lower BMI, and HDL-cholesterol, renin with CAD higher glycated hemoglobin HbA1c, and smoking.ConclusionsIn a CCTA-based cohort, four proteins, involved in opposing vascular processes (healing vs. adverse remodeling), are specifically associated with low CAD burden in high CV-risk individuals (high MYO and C-C-22) and high CAD burden in low-risk subjects (high PS-3 and PAF-AH), in interaction with BMI, smoking, diabetes, HDL-cholesterol, and HbA1c. These findings could contribute to a deeper understanding of the atherosclerotic process beyond traditional risk profile assessment and potentially constitute new treatment targets.

Section: Discussionmentioning

confidence: 98%

Differential Proteomics of Cardiovascular Risk and Coronary Artery Disease in Humans

Manca

Front. Cardiovasc. Med.

et al. 2022

“… 23 In contrast, CCB did not affect PRA. Subanalysis of the Multiethnic Study of Atherosclerosis (MESA) study revealed that PRA is one of the primary risks for atherosclerotic vascular disease (ASCVD), 26 with plasma aldosterone independent of ASCVD incidence. In contrast, aldosterone agonism is suggested as another risk factor for aortic dissection and rupture.…”

Section: Discussionmentioning

confidence: 99%

“…markers associated with AAA growth, and there is no consensus regarding circulating markers introduced into clinical practice. In the present study, we selected the biomarkers associated with AAA pathophysiology, such as vascular remodeling (MMPs, TIMP, cystatin C), RAS system (PRA, plasma aldosterone, plasma angiotensin II), inflammation (hs-CRP), cell growth/proliferation (TGFβ), or oxidative stress (MDA-LDL), to understand the Subanalysis of the Multiethnic Study of Atherosclerosis (MESA) study revealed that PRA is one of the primary risks for atherosclerotic vascular disease (ASCVD), 26 with plasma aldosterone independent of ASCVD incidence. In contrast, aldosterone agonism is suggested as another risk factor for aortic dissection and rupture.…”

Section: Secondary Outcomesmentioning

confidence: 99%

Role of Common Antihypertensives in the Growth of Abdominal Aortic Aneurysm at the Presurgical Stage

Mitsui,

Bando,

Hirakawa

et al. 2023

Circ Rep

Background: Whether drug therapy slows the growth of abdominal aortic aneurysms (AAAs) in the Japanese population remains unknown. Methods and Results: In a multicenter prospective open-label study, patients with AAA at the presurgical stage (mean [±SD] AAA diameter 3.27±0.58 cm) were randomly assigned to treatment with candesartan (CAN; n=67) or amlodipine (AML; n=64) considering confounding factors (statin use, smoking, age, sex, renal function), with effects of blood pressure control minimized setting a target control level. The primary endpoint was percentage change in AAA diameter over 24 months. Secondary endpoints were changes in circulating biomarkers (high-sensitivity C-reactive protein [hs-CRP], malondialdehyde–low-density lipoprotein, tissue-specific inhibitor of metalloproteinase-1, matrix metalloproteinase [MMP] 2, MMP9, transforming growth factor-β1, plasma renin activity [PRA], angiotensin II, aldosterone). At 24 months, percentage changes in AAA diameter were comparable between the CAN and AML groups (8.4% [95% CI 6.23–10.59%] and 6.5% [95% CI 3.65–9.43%], respectively; P=0.23]. In subanalyses, AML attenuated AAA growth in patients with comorbid chronic kidney disease (CKD; P=0.04) or systolic blood pressure (SBP) <130 mmHg (P=0.003). AML exhibited a definite trend for slowing AAA growth exclusively in never-smokers (P=0.06). Among circulating surrogate candidates for AAA growth, PRA (P=0.02) and hs-CRP (P=0.001) were lower in the AML group. Conclusions: AML may prevent AAA growth in patients with CKD or lower SBP, associated with a decline in PRA and circulating hs-CRP.

“…As the initial and rate-limiting step of the classical RAAS, renin is an aspartyl protease mainly produced by the juxtaglomerular cells of the renal afferent arteriole ( Shigemura et al, 2019 ). Its plasma activity is associated with greater burden of coronary artery disease ( Unkart et al, 2020 ). The synthesis and release of renin are stimulated by three major mechanisms: the decrease of sodium chloride concentration in the macula dense and perfusion pressure as sensed by renal baroreceptors; and the activation of β-adrenergic receptors in juxtaglomerular cells by catecholamines ( Gomez and Sequeira-Lopez, 2018 ).…”

Section: Pathophysiology Of Post-mi Cardiac Fibrosismentioning

confidence: 99%

Post-myocardial infarction fibrosis: Pathophysiology, examination, and intervention

Yin

Pan

et al. 2023

Front. Pharmacol.

Cardiac fibrosis plays an indispensable role in cardiac tissue homeostasis and repair after myocardial infarction (MI). The cardiac fibroblast-to-myofibroblast differentiation and extracellular matrix collagen deposition are the hallmarks of cardiac fibrosis, which are modulated by multiple signaling pathways and various types of cells in time-dependent manners. Our understanding of the development of cardiac fibrosis after MI has evolved in basic and clinical researches, and the regulation of fibrotic remodeling may facilitate novel diagnostic and therapeutic strategies, and finally improve outcomes. Here, we aim to elaborate pathophysiology, examination and intervention of cardiac fibrosis after MI.