Pushpakumar, S.; Singh, M.; Zheng, Y.; Akinterinwa, O.E.; Mokshagundam, S.P.L.; Sen, U.; Kalra, D.K.; Tyagi, S.C. Renal Denervation Helps Preserve the Ejection Fraction by Preserving Endocardial-Endothelial Function during Heart Failure. Int. J. Mol. Sci.2023, 24, 7302.
Pushpakumar, S.; Singh, M.; Zheng, Y.; Akinterinwa, O.E.; Mokshagundam, S.P.L.; Sen, U.; Kalra, D.K.; Tyagi, S.C. Renal Denervation Helps Preserve the Ejection Fraction by Preserving Endocardial-Endothelial Function during Heart Failure. Int. J. Mol. Sci. 2023, 24, 7302.
Pushpakumar, S.; Singh, M.; Zheng, Y.; Akinterinwa, O.E.; Mokshagundam, S.P.L.; Sen, U.; Kalra, D.K.; Tyagi, S.C. Renal Denervation Helps Preserve the Ejection Fraction by Preserving Endocardial-Endothelial Function during Heart Failure. Int. J. Mol. Sci.2023, 24, 7302.
Pushpakumar, S.; Singh, M.; Zheng, Y.; Akinterinwa, O.E.; Mokshagundam, S.P.L.; Sen, U.; Kalra, D.K.; Tyagi, S.C. Renal Denervation Helps Preserve the Ejection Fraction by Preserving Endocardial-Endothelial Function during Heart Failure. Int. J. Mol. Sci. 2023, 24, 7302.
Abstract
Although renal denervation (RDN) protects against hypertension, hypertrophy, and heart failure (HF), it is not clear whether RDN preserves ejection fraction (EF) during heart failure (HFpEF). To test this hypothesis, we simulated chronic congestive cardiopulmonary heart failure (CHF) by creating aorta-vena cava fistula (AVF) in C57BL/6J wild type (WT) mice. There are four ways to create experimental CHF: (1) myocardial infarction (MI) which is basically ligating coronary by instrumenting and injuring the heart; (2) trans-aortic constriction (TAC), although it mimics systematic hypertension but TAC again constricts aorta on top of the heart and exposes the heart; (3) acquired CHF such as by dietary factors, diabetes/salt diets etc. but it is multifactorial, and finally (4) AVF, which is the only one wherein AVF is created ~1cm below the kidney where the aorta and vena cava share the common middle-wall. By creating fistula, the red blood enters vena cava without an injury to the heart. This model mimics CHF such as during aging where with age the preload keeps increasing than the aging heart can pump out due to the weakened cardiac myocytes. This also involves the right ventricle to lung to left ventricle flow, thus creating congestion. The heart in AVF goes to transition from preserved to reduced EF (i.e., HFpEF to HFrEF). In fact, there are more models of volume overload, such as the pacing-induced and mitral valve regurgitation but these are also injurious models. Our lab is one of the original labs in creating and studying the AVF phenotype. The RDN was created by treating the cleaned bilateral renal artery. After 6 weeks, blood, heart, and renal samples were analyzed for exosome, cardiac regeneration markers and renal cortex proteinases. Cardiac function was analyzed by echocardiogram (ECHO). Fibrosis was analyzed with trichrome staining. The results suggested that there was robust increase in exosomes’ level in AVF blood, suggesting compensatory systemic response during AVF-CHF. During AVF there was no change in cardiac eNOS, Wnt1 and β-catenin, however; during RDN there was robust increase in eNOS, Wnt1 and β-catenin compared to the sham group. As expected in HFpEF there was perivascular fibrosis, hypertrophy and pEF. Interestingly, increased levels of eNOS suggested that despite fibrosis, the NO generation was higher that most likely contributed to pEF during HF. The RDN intervention revealed an increase in renal cortical caspase 8 and a decrease in caspase 9. Since caspase 8 is protective and caspase 9 is apoptotic, we suggest that RDN protects against renal stresses, and apoptosis. Our findings also suggest that RDN is cardioprotective during HFpEF via the preservation of eNOS and accompanied endocardial-endothelial function.
Keywords
Antioxidant molecules; Cardiac health; Mechanism of heart failure; Cardiac activity
Subject
Medicine and Pharmacology, Cardiac and Cardiovascular Systems
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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