Renin–Angiotensin–Aldosterone System: Friend or Foe—The Matter of Balance. Insight on History, Therapeutic Implications and COVID-19 Interactions

Šimko, Fedor; Hrenak, Jaroslav; Adamcová, Michaela; Paulis, Ludovít

doi:10.3390/ijms22063217

Cited by 20 publications

(25 citation statements)

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“…However, its chronic activation may impair cardiac function and structure both via hemodynamic overload as well as direct trophic action on cardiac and vascular tissues. The deleterious effect of chronic RAS activation is reflected by the success of RAS inhibition in a variety of cardiovascular pathologies [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ].…”

Section: The Renin–angiotensin Systemmentioning

confidence: 99%

“…ACE inhibition does not entirely inhibit Ang II biosynthesis, as other proteases such as kallikrein, cathepsin G, heart chymase, and elastase-2 also converting Ang I to Ang II [14,15]. Moreover, Ang I and Ang II are alternatively cleaved into Ang (1)(2)(3)(4)(5)(6)(7)(8)(9) and Ang (1-7), respectively, by the action of the ACE2 enzyme, although Ang II is significantly preferred over Ang I as a substrate [16][17][18]. Ang (1-7) can also be formed from Ang (1)(2)(3)(4)(5)(6)(7)(8)(9) by ACE or directly from Ang I by endopeptidases such as neprilysin, or from Ang II by prolylcarboxypeptidase [19].…”

Section: Alternative Pathways Of Rasmentioning

confidence: 99%

“…Moreover, Ang I and Ang II are alternatively cleaved into Ang (1)(2)(3)(4)(5)(6)(7)(8)(9) and Ang (1-7), respectively, by the action of the ACE2 enzyme, although Ang II is significantly preferred over Ang I as a substrate [16][17][18]. Ang (1-7) can also be formed from Ang (1)(2)(3)(4)(5)(6)(7)(8)(9) by ACE or directly from Ang I by endopeptidases such as neprilysin, or from Ang II by prolylcarboxypeptidase [19]. Increased ACE2 expression attenuates Ang II-induced cardiac hypertrophy while its reduced expression is associated with impaired cardiac contractility and hypertension development [20,21].…”

Section: Alternative Pathways Of Rasmentioning

confidence: 99%

“…The beneficial effects of ACE inhibitors and AT1R blockers (ARB) are at least partially mediated through the increased accumulation of Ang (1)(2)(3)(4)(5)(6)(7). ACE inhibition leads to Ang I accumulation and its increased conversion to Ang (1-7) [24].…”

Section: Alternative Pathways Of Rasmentioning

confidence: 99%

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The Impact of microRNAs in Renin–Angiotensin-System-Induced Cardiac Remodelling

Adamcová

Kawano

Šimko

2021

IJMS

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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

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Section: The Renin–angiotensin Systemmentioning

confidence: 99%

Section: Alternative Pathways Of Rasmentioning

confidence: 99%

Section: Alternative Pathways Of Rasmentioning

confidence: 99%

Section: Alternative Pathways Of Rasmentioning

confidence: 99%

See 2 more Smart Citations

The Impact of microRNAs in Renin–Angiotensin-System-Induced Cardiac Remodelling

Adamcová

Kawano

Šimko

2021

IJMS

Self Cite

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“…2). When SARS-CoV-2 is attached to ACE2 its expression is reduced, thus causing lung injury and pneumonia [83,84,175]. Vitamin D3 is a negative RAS modulator by inhibition of renin expression and stimulation of ACE2 expression.…”

Section: Introductionmentioning

confidence: 99%

COVID-19 mortality risk correlates inversely with vitamin D3 status, and a mortality rate close to zero could theoretically be achieved at 50 ng/ml 25(OH)D3: Results of a systematic review and meta-analysis

Borsche

Glauner

Mendel

2021

Preprint

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Background Much research shows that blood calcidiol (25(OH)D3) levels correlate strongly with SARS-CoV-2 infection severity. There is open discussion regarding whether low D3 is caused by the infection or if deficiency negatively affects immune defense. The aim of this study was to collect further evidence on this topic. Methods Systematic literature search was performed to identify retrospective cohort as well as clinical studies on COVID-19 mortality rates vs. D3 blood levels. Mortality rates from clinical studies were corrected for age, sex and diabetes. Data was analyzed using correlation and linear regression. Results One population study and seven clinical studies were identified, which reported D3 blood levels pre-infection or on the day of hospital admission. They independently showed a negative Pearson correlation of D3 levels and mortality risk (r(17)=-.4154, p=.0770/r(13)=-.4886, p=.0646). For the combined data, median (IQR) D3 levels were 23.2 ng/ml (17.4 – 26.8), and a significant Pearson correlation was observed (r(32)=-.3989, p=.0194). Regression suggested a theoretical point of zero mortality at approximately 50 ng/ml D3. Conclusions The two datasets provide strong evidence that low D3 is a predictor rather than a side effect of the infection. Despite ongoing vaccinations, we recommend raising serum 25(OH)D levels to above 50 ng/ml to prevent or mitigate new outbreaks due to escape mutations or decreasing antibody activity.

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The association between vitamin D intake with inflammatory and biochemical indices and mortality in critically ill patients with COVID‐19: A case‐control study

Rabbani

Ahmadzadeh

Hajipour

et al. 2023

Immunity Inflam & Disease

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Background The coronavirus disease‐2019 (COVID‐19) has become a worldwide health issue with widespread hospitalization and dependence on the intensive care unit (ICU). Vitamin D has a key role in modulating immune cells and modulating the inflammatory responses. This study aimed to investigate the association of vitamin D supplementation with inflammatory, biochemical, and mortality indices in critically ill patients with COVID‐19. Methods This case‐control study was conducted on critically ill COVID‐19 patients hospitalized in the ICU including the survived >30 day patients as the case group and dead patients as the control group. The status of vitamin D supplementation and inflammatory and biochemical indices of the patients were retrieved from the medical records. Logistic regression method was used to assess the association between 30 days survival and vitamin D supplement intake. Results Compared to the group of COVID‐19 patients who died in <30 day, the survived patients had a lower eosinophile level (2.2 ± 0.5 vs. 6 ± 0.0, p < .001) and higher vitamin D supplementation duration (9 ± 4.4 vs. 3.3 ± 1.9 day, p = .001). Vitamin D supplementation had a positive association with survival in COVID‐19 patients (OR: 1.98, 95% CI: 1.15−3.40, p < .05). The association remained significant after adjustments fot age, sex, underlying diseases, and smoking. Conclusion Vitamin D supplementation in critically ill patients with COVID‐19 has the potential to increase survivability within the first 30 days of hospitalization.

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Renin–Angiotensin–Aldosterone System: Friend or Foe—The Matter of Balance. Insight on History, Therapeutic Implications and COVID-19 Interactions

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

Cited by 20 publications

References 40 publications

The Impact of microRNAs in Renin–Angiotensin-System-Induced Cardiac Remodelling

The Impact of microRNAs in Renin–Angiotensin-System-Induced Cardiac Remodelling

COVID-19 mortality risk correlates inversely with vitamin D3 status, and a mortality rate close to zero could theoretically be achieved at 50 ng/ml 25(OH)D3: Results of a systematic review and meta-analysis

The association between vitamin D intake with inflammatory and biochemical indices and mortality in critically ill patients with COVID‐19: A case‐control study

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