Sodium butyrate attenuates angiotensin II‐induced cardiac hypertrophy by inhibiting COX2/PGE2 pathway via a HDAC5/HDAC6‐dependent mechanism

Abstract

Sodium butyrate (NaBu) is reported to play important roles in a number of chronic diseases. The present work is aimed to investigate the effect of NaBu on angiotensin II (Ang II)‐induced cardiac hypertrophy and the underlying mechanism in in vivo and in vitro models. Sprague Dawley rats were infused with vehicle or Ang II (200 ng/kg/min) and orally administrated with or without NaBu (1 g/kg/d) for two weeks. Cardiac hypertrophy parameters and COX2/PGE2 pathway were analysed by real‐time PCR, ELISA, immunostaining and Western blot. The cardiomyocytes H9C2 cells were used as in vitro model to investigate the role of NaBu (2 mmol/L) in inhibition of Ang II‐induced cardiac hypertrophy. NaBu significantly attenuated Ang II‐induced increase in the mean arterial pressure. Ang II treatment remarkably increased cardiac hypertrophy as indicated by increased ratio of heart weight/body weight and enlarged cardiomyocyte size, extensive fibrosis and inflammation, as well as enhanced expression of hypertrophic markers, whereas hearts from NaBu‐treated rats exhibited a significant reduction in these hypertrophic responses. Mechanistically, NaBu inhibited the expression of COX2/PGE2 along with production of ANP and phosphorylated ERK (pERK) stimulated by Ang II in in vivo and in vitro, which was accompanied by the suppression of HDAC5 and HDAC6 activities. Additionally, knocking down the expression of HDAC5 and HDAC6 via gene‐editing strategy dramatically blocked Ang II‐induced hypertrophic responses through COX2/PGE2 pathway. These results provide solid evidence that NaBu attenuates Ang II‐induced cardiac hypertrophy by inhibiting the activation of COX2/PGE2 pathway in a HDAC5/HDAC6‐dependent manner.

ELABELA attenuates deoxycorticosterone acetate/salt-induced hypertension and renal injury by inhibition of NADPH oxidase/ROS/NLRP3 inflammasome pathway

“…For quantitative reverse transcription PCR (qRT-PCR), total RNA isolation was performed as previously described 33 . Reverse transcription and SYBR green based quantitative polymerase chain reaction were performed as the manufacturer's instructions (TsingKe Biological Technology, TSE202).…”

Multiscale model of heart growth during pregnancy: Integrating mechanical and hormonal signaling

“…8, Fig. 4B) simultaneously using reported relative changes in LV mass from VO [29,42,48,[55][56][57][58][59][60] and AngII infusion [19][20][21][22][23][24][25][26] experiments in rats. To simulate VO, we set the circulatory parameters to the fitted acute VO values and maintained them throughout growth.…”

“…Notably, the Stretch input increased acutely and gradually decreased in our VO simulations while it remained relatively constant near baseline for AngII, E2, and P4. [19][20][21][22][23][24][25][26], Progesterone (P4) infusion [28], and Estrogen (E2) infusion [53,[64][65][66]. A.)…”

“…An increase in aortic resistance due to constriction (pressure overload, PO) leads to mass increase and wall thickening, while an increase in cardiac output due to an arteriovenous fistula or valvular regurgitation (volume overload, VO) leads to mass increase and LV cavity dilation. Infusion of isoproterenol leads to LV mass increase [7][8][9][10][11][12][13][14][15][16][17][18], as does infusion with angiotensin [19][20][21][22][23][24][25][26]. Pregnancy hormones also influence heart growth.…”

Honokiol ameliorates angiotensin II‐induced hypertension and endothelial dysfunction by inhibiting HDAC6‐mediated cystathionine γ‐lyase degradation

“…17 In similar contexts, HDAC6 has been proposed as a therapeutic target for treatment of cardiovascular diseases. [15][16][17][18][19] We also recently reported that tubastatin A, an HDAC6-specific inhibitor, could increase CSE acetylation and enhance its protein levels and H 2 S production, thereby helping to attenuate the vasoconstriction and hypertension induced by AngII. 20 Moreover, HDAC6, a member of the class IIb HDAC family, exhibits distinct characters compared to other HDAC family members in that it has unique specificity for protein deacetylation of non-histone substrates such as α-tubulin, cortactin and heat-shock protein 90.…”