Attenuation of myocardial fibrosis with curcumin is mediated by modulating expression of angiotensin II AT1/AT2 receptors and ACE2 in rats

Abstract

Curcumin is known to improve cardiac function by balancing degradation and synthesis of collagens after myocardial infarction. This study tested the hypothesis that inhibition of myocardial fibrosis by curcumin is associated with modulating expression of angiotensin II (Ang II) receptors and angiotensin-converting enzyme 2 (ACE2). Male Sprague Dawley rats were subjected to Ang II infusion (500 ng/kg/min) using osmotic minipumps for 2 and 4 weeks, respectively, and curcumin (150 mg/kg/day) was fed by gastric gavage during Ang II infusion. Compared to the animals with Ang II infusion, curcumin significantly decreased the mean arterial blood pressure during the course of the observation. The protein level of the Ang II type 1 (AT1) receptor was reduced, and the Ang II type 2 (AT2) receptor was up-regulated, evidenced by an increased ratio of the AT2 receptor over the AT1 receptor in the curcumin group (1.2±0.02%) vs in the Ang II group (0.7±0.03%, P<0.05). These changes were coincident with less locally expressed AT1 receptor and enhanced AT2 receptor in the intracardiac vessels and intermyocardium. Along with these modulations, curcumin significantly decreased the populations of macrophages and alpha smooth muscle actin-expressing myofibroblasts, which were accompanied by reduced expression of transforming growth factor beta 1 and phosphorylated-Smad2/3. Collagen I synthesis was inhibited, and tissue fibrosis was attenuated, as demonstrated by less extensive collagen-rich fibrosis. Furthermore, curcumin increased protein level of ACE2 and enhanced its expression in the intermyocardium relative to the Ang II group. These results suggest that curcumin could be considered as an add-on therapeutic agent in the treatment of fibrosis-derived heart failure patient who is intolerant of ACE inhibitor therapy.

Curcumin (a constituent of turmeric): New treatment option against COVID‐19

“…Dietary administration of curcumin (150 mg kg -1 day -1 , gavage during Ang II infusion) decreased the protein level of the AT1 receptor and enhanced the expression of the AT2 receptor/ACE2 and results in the attenuation of myocardial fibrosis in a rat model of angiotensin II infusion (Pang et al, 2015). These data suggest that similar events happen in the lung tissues to prevent fibrosis.…”

Potential effects of curcumin in the treatment of COVID‐19 infection

“…However, the reduction of ACE2 activity is detrimental to the heart, since it contributes to cardiac dysfunction, partly due to increased stimulation of the AT1 receptor by angiotensin II (Yamamoto et al, 2006). Pang et al demonstrated that curcumin significantly decreases mean arterial blood pressure and improves cardiac fibrosis in rats through upregulation of angiotensin II type II receptor, down-regulation of angiotensin II type I receptor, and increase of ACE2 in the myocardium (Pang et al, 2015).…”

Angiotensin II triggers RIPK3-MLKL-mediated necroptosis by activating the Fas/FasL signaling pathway in renal tubular cells

“…Therefore, we speculate that AngII mediates renal tubular cell necroptosis via its receptors and the Fas/FasL signaling pathway. A previous study showed that there was reciprocal expression between AT1R and AT2R in response to Ang II infusion, with evident AT1R upregulation and AT2R downregulation [36,37]. However, the current data clearly challenge that concept.…”