Renal sympathetic denervation improves myocardial apoptosis in rats with isoproterenol‑induced heart failure by downregulation of tumor necrosis factor‑α and nuclear factor‑κB

Abstract

Chronic congestive heart failure (CHF) is the end outcome of organic heart diseases and one of the major diseases harmful to human health. Renal sympathetic denervation (RSD) is the anatomical basis of transcatheter renal sympathetic nerve ablation within the renal artery. To date, the roles of norepinephrine and angiotensin II (Ang II) in myocardial apoptosis and their underlying mechanisms have not been well explored. The aim of the present study was to verify the hypothesis that RSD is likely to inhibit myocardial apoptosis by inhibiting the release of norepinephrine and Ang II. An isoproterenol-induced CHF rat model was established, and the effects of RSD on myocardial apoptosis were examined using flow cytometry and TUNEL staining. The expression of factors associated with myocardial apoptosis, including p53, tumor necrosis factor-α (TNF-α), nuclear factor-κB (NF-κB), caspase-2 and −3, were measured using quantitative polymerase chain reaction and western blot analysis. The results indicated that the mRNA levels of p53, TNF-α, NF-κB, caspase-2 and −3 were significantly reduced in the myocardial tissues of rats in the CHF+RSD group when compared with the levels in the CHF+sham group (P<0.01 for all). In addition, the protein levels of p53, TNF-α, NF-κB and caspases-2 and −3 were decreased by 42.6, 41.3, 46.7, 30.0 and 35.8%, respectively, in myocardial tissues of rats in the CHF+RSD group in comparison with the CHF+sham group (P<0.01 for all). Furthermore, myocardial apoptosis was improved in rats in the CHF+RSD group compared with that in the CHF+sham group (P<0.01). In conclusion, the present study provides a theoretical basis for application of RSD in the treatment of CHF.

Immediate Renal Denervation After Acute Myocardial Infarction Mitigates the Progression of Heart Failure via the Modulation of IL-33/ST2 Signaling

“…In our study, we observed reduced levels of sST2 after AMI by immediate RDN, together with changes in IL-33-related remodeling pathways, including reduced activation of NF-κb and expression of TGFβ. The inhibitory effect of RDN on NFκb has been demonstrated previously, which further supports our findings that RDN exerts anti-remodeling effects by the reduction of sST2 and the subsequent modulation of the IL-33/ST2 pathway (34,35).…”

Renal Sympathetic Nerve-Derived Signaling in Acute and Chronic Kidney Diseases

“…In cultured kidney proximal tubule cells, NE treatment increases poly (ADP-ribose) polymerase 1 (PARP1) and cleaved caspase-3 expression, which is reduced by co-treatment with caspase-3 inhibitor [59]. Consistent with our data, RDNx inhibits renal sympathetic activation, significantly attenuating the expression levels of p53, TNF-α, NF-κB, caspase-2 and -3, and improving apoptosis [146]. On the other hand, activation of α 2 -AR with dexmedetomidine, α 2 -AR agonist attenuates renal cell apoptosis and renal tubule impairment by inhibiting mitochondrial apoptosis pathways in the sepsis-or I/R-induced injury model, which may be effective by regulating NE release [147][148][149].…”

Allylmethylsulfide, a Sulfur Compound Derived from Garlic, Attenuates Isoproterenol-Induced Cardiac Hypertrophy in Rats

“…To investigate the effect of AMS on apoptosis, we have studied the protein expression of caspases. Pathological enlargement of the myocardium with isoproterenol results in activation of programmed cell death, compromised contractile function, and eventually heart failure [39]. Besides apoptosis, caspases play an important role in cardiac inflammation.…”