Renin and cardiovascular disease: Worn-out path, or new direction

Alreja, Gaurav; Joseph, Jacob

doi:10.4330/wjc.v3.i3.72

Cited by 9 publications

(6 citation statements)

References 100 publications

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“…This relatively small decrease in MAP may be due to the lack of significant downregulation in renal angiotensinogen or renin expression in EMPA-treated PCOS rats. The conversion of angiotensinogen to angiotensin I by renin is the rate-limiting step of the RAS [ 38 ]. Woods et al showed that decreased angiotensinogen was associated with decreased BP by SGLT2 inhibition in males in a T2DM model [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Impact of SGLT-2 Inhibition on Cardiometabolic Abnormalities in a Rat Model of Polycystic Ovary Syndrome

Pruett

Fernandez

Everman

et al. 2021

IJMS

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Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women. PCOS is characterized by hyperandrogenism and ovulatory dysfunction. Women with PCOS have a high prevalence of obesity, insulin resistance (IR), increased blood pressure (BP), and activation of the renin angiotensin system (RAS). Effective evidence-based therapeutics to ameliorate the cardiometabolic complications in PCOS are lacking. The sodium-glucose cotransporter-2 (SGLT2) inhibitor Empagliflozin (EMPA) reduces BP and hyperglycemia in type 2 diabetes mellitus. We hypothesized that hyperandrogenemia upregulates renal SGLT2 expression and that EMPA ameliorates cardiometabolic complications in a hyperandrogenemic PCOS model. Four-week-old female Sprague Dawley rats were treated with dihydrotestosterone (DHT) for 90 days, and EMPA was co-administered for the last three weeks. DHT upregulated renal SGLT2, SGLT4, and GLUT2, but downregulated SGLT3 mRNA expression. EMPA decreased DHT-mediated increases in fat mass, plasma leptin, and BP, but failed to decrease plasma insulin, HbA1c, or albuminuria. EMPA decreased DHT-mediated increase in renal angiotensin converting enzyme (ACE), angiotensin converting enzyme 2 (ACE2), and angiotensin II type 1 receptor (AGT1R) mRNA and protein expression. In summary, SGLT2 inhibition proved beneficial in adiposity and BP reduction in a hyperandrogenemic PCOS model; however, additional therapies may be needed to improve IR and renal injury.

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Section: Discussionmentioning

confidence: 99%

Impact of SGLT-2 Inhibition on Cardiometabolic Abnormalities in a Rat Model of Polycystic Ovary Syndrome

Pruett

Fernandez

Everman

et al. 2021

IJMS

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“…As two antihypertensives in the involvement of renin angiotensin system (RAS), they have similar mechanisms. ACEIs could reduce production of angiotensin (Ang) II by inhibiting angiotensin converting enzyme, a key enzyme affecting the transformation from angiotensin I to angiotensin II [36] . Also, the inhibition of the angiotensin converting enzyme also increased bradykinin production [37] .…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II Receptor Blockers Improve Peripheral Endothelial Function: A Meta-Analysis of Randomized Controlled Trials

et al. 2014

PLoS ONE

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Objective(s)Several studies have assessed the effect of angiotensin II receptor blockers (ARBs) on peripheral endothelial dysfunction as measured by flow-mediated vasodilatation (FMD), a widely-used indicator for endothelial function. We conducted a meta-analysis to investigate the effect in comparison to placebo or no treatment and other antihypertensives.MethodsMEDLINE, Cochrane library and EMBASE were searched to September 2013 for randomized controlled trials (RCTs) that assessed the effect of ARBs versus placebo or no treatment and other antihypertensives (angiotensin-converting enzyme inhibitors (ACEIs), calcium channel blockers (CCBs), β-blockers, diuretics) by forearm FMD. Furthermore, we also use meta-regression to analyze the relationship between the endothelial function and the duration of ARBs treatments.ResultsIn 11 trials including 590 patients, ARBs (n = 315) significantly improved FMD (1.36%, 95% confidence internal [CI]:1.28 to 1.44) versus placebo or no treatment (n = 275). In 16 trials that included 1028 patients, ARBs (n = 486) had a significant effect (0.59%, 95% CI: 0.25 to 0.94) on FMD when compared with other antihypertensives (n = 542). In 8 trials, ARBs (n = 174) had no significant effect (−0.14%, 95% CI: −0.32 to 0.03) compared with ACEI (n = 173). Compared with others, the benefits of ARBs, respectively, were 1.67% (95% CI: 0.65 to 0.93) in 7 trials with CCBs, 0.79% (95% CI: 0.42 to 1.01) with β-blockers in 3 trials and 0.9% (95% CI: 0.77 to 1.03) with diuretics in 3 trials. Importantly, we found ARBs were less effective in a long time span (95% CI: −1.990 to −0.622) than the first 6 months (95% CI: −0.484 to 0.360).ConclusionsThis study shows that ARBs improve peripheral endothelial function and are superior to CCBs, β-blockers and diuretics. However, the effect couldn't be maintained for a long time. In addition, there was no significant difference between ARBs and ACEI.

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“…ACEIs improve endothelial function by reducing the production of angiotensin II by inhibiting angiotensin converting enzyme, a key enzyme affecting the transformation from angiotensin I to angiotensin II and increasing bradykinin production (71,72). A meta-analysis of randomized controlled trials demonstrated that ACEIs improve peripheral endothelial function and are superior to other anti-hypertensive drugs including calcium channel blockers and β-blockers (73).…”

Section: Therapeutic Approachesmentioning

confidence: 99%

Endothelial dysfunction and coronary artery disease

Matsuzawa

Lerman

2014

Coronary Artery Disease

203

134

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Progress in modification of conventional coronary risk factors and lifestyle behavior reduced atherosclerotic coronary artery disease incidence, nonetheless it continues to be the leading cause of mortality in the world. It might be attributed to the defective risk stratifying and prevention strategy for coronary artery disease. Atherosclerotic coronary artery disease risk is estimated based on identifying and quantifying only traditional risk factors in current clinical settings, it does not consider non-traditional risk factors. In addition, most of prevailing therapies for atherosclerosis are targeted for traditional risk factors rather than atherosclerosis itself. It is desirable to have a methodology which can directly assess the activity of atherogenesis at each moment. Endothelial function is an integrated index of all atherogenic and atheroprotective factors present in an individual including non-traditional and heretofore unknown factors, and is reported to have additional predictive value for future cardiovascular events to traditional risk factors. Moreover, endothelial function has a pivotal role in all phases of atherosclerosis, from initiation to atherothrombotic complication, and is reversible at every phase, indicating that endothelial function-guided therapies might be effective and feasible in cardiovascular practice. Thus, the introduction of endothelial function testing into clinical practice might enable us to innovate individualized cardiovascular medicine. In this review, we summarize the current knowledge on the contribution of endothelial dysfunction to atherogenesis and review methods that assess endothelial function. Finally we focus on the effects of major anti-atherosclerotic disease therapies on endothelial function, and argue the possibility of non-invasive assessment of endothelial function aiming at individualized cardiovascular medicine.

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Renin and cardiovascular disease: Worn-out path, or new direction

Cited by 9 publications

References 100 publications

Impact of SGLT-2 Inhibition on Cardiometabolic Abnormalities in a Rat Model of Polycystic Ovary Syndrome

Impact of SGLT-2 Inhibition on Cardiometabolic Abnormalities in a Rat Model of Polycystic Ovary Syndrome

Angiotensin II Receptor Blockers Improve Peripheral Endothelial Function: A Meta-Analysis of Randomized Controlled Trials

Endothelial dysfunction and coronary artery disease

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