Right versus left ventricular remodeling in heart failure due to chronic volume overload.
Right versus left ventricular remodeling in heart failure due to chronic volume overload.
复制标题
DOI：
10.1038/s41598-021-96618-8
复制
发表时间：
2021-08-24
影响因子：
4.6
通讯作者：
Melenovsky V
中科院分区：
文献类型：
--
作者：
Havlenova T;Skaroupkova P;Miklovic M;Behounek M;Chmel M;Jarkovska D;Sviglerova J;Stengl M;Kolar M;Novotny J;Benes J;Cervenka L;Petrak J;Melenovsky V
心衰（HF）患者右心室（RV）功能障碍的机制尚不清楚。RV对体积过载（VO）的响应是HF的一个常见因素，但很少被研究。目的是确定慢性VO反应的室间差异。大鼠采用主动脉-腔静脉瘘(ACF)/假手术诱导VO。24周后观察大鼠左室、左室功能、基因表达及蛋白质组学变化。ACF导致双室扩张，收缩功能障碍和肥厚影响相对较多的RV。与左心室相比，左心室后负荷增加导致左心室行程功增量增大。两个ACF心室均表现出心肌应激和代谢基因的上调。大多数蛋白在两个心室中对左心室的反应方向相似，但右心室的表达变化更为明显（pslope < 0.001）。上调最多的是细胞外基质（POSTN、NRAP、TGM2、CKAP4）、细胞粘附（NCAM、NRAP、XIRP2）和细胞骨架蛋白（FHL1、CSRP3）以及碳水化合物（PKM）或去甲肾上腺素（MAOA）代谢酶。下调的是MYH6和FAO酶。因此，当暴露于相同的VO时，两个心室表现出相似的应激和代谢标志物上调。与左室相比，ACF左室相对较大的反应可能是由合并肺动脉高压引起的。没有证据支持RV室对VO的特异性蛋白表达调节。
Mechanisms of right ventricular (RV) dysfunction in heart failure (HF) are poorly understood. RV response to volume overload (VO), a common contributing factor to HF, is rarely studied. The goal was to identify interventricular differences in response to chronic VO. Rats underwent aorto-caval fistula (ACF)/sham operation to induce VO. After 24 weeks, RV and left ventricular (LV) functions, gene expression and proteomics were studied. ACF led to biventricular dilatation, systolic dysfunction and hypertrophy affecting relatively more RV. Increased RV afterload contributed to larger RV stroke work increment compared to LV. Both ACF ventricles displayed upregulation of genes of myocardial stress and metabolism. Most proteins reacted to VO in a similar direction in both ventricles, yet the expression changes were more pronounced in RV (pslope: < 0.001). The most upregulated were extracellular matrix (POSTN, NRAP, TGM2, CKAP4), cell adhesion (NCAM, NRAP, XIRP2) and cytoskeletal proteins (FHL1, CSRP3) and enzymes of carbohydrate (PKM) or norepinephrine (MAOA) metabolism. Downregulated were MYH6 and FAO enzymes. Therefore, when exposed to identical VO, both ventricles display similar upregulation of stress and metabolic markers. Relatively larger response of ACF RV compared to the LV may be caused by concomitant pulmonary hypertension. No evidence supports RV chamber-specific regulation of protein expression in response to VO.
登录
查看更多内容
影响因子：
48
作者：
Huber W;Carey VJ;Gentleman R;Anders S;Carlson M;Carvalho BS;Bravo HC;Davis S;Gatto L;Girke T;Gottardo R;Hahne F;Hansen KD;Irizarry RA;Lawrence M;Love MI;MacDonald J;Obenchain V;Oleś AK;Pagès H;Reyes A;Shannon P;Smyth GK;Tenenbaum D;Waldron L;Morgan M
通讯作者：
Morgan M
DOI：
10.1152/ajpheart.00180.2013
发表时间：
2013-08-01
影响因子：
4.8
作者：
Borgdorff, Marinus A. J.;Bartelds, Beatrijs;Berger, Rolf M. F.
通讯作者：
Berger, Rolf M. F.
影响因子：
18.2
作者：
Bartelds, Beatrijs;Borgdorff, Marinus A.;Berger, Rolf M. F.
通讯作者：
Berger, Rolf M. F.
影响因子：
5
作者：
Guggilam, Anuradha;Hutchinson, Kirk R.;Lucchesi, Pamela A.
通讯作者：
Lucchesi, Pamela A.
影响因子：
37.8
作者：
Aung, Nay;Vargas, Jose D.;Petersen, Steffen E.
通讯作者：
Petersen, Steffen E.