看片视频

Sign-up for our newsletter

Publication

Knockout of insulin receptors in cardiomyocytes attenuates coronary arterial dysfunction induced by pressure overload.

Authors Symons JD, Hu P, Yang Y, Wang X, Zhang QJ, Wende AR, Sloan CL, Sena S, Abel ED, Litwin SE Submitted By E. Dale Abel on 5/2/2011 Status Published Journal American journal of physiology. Heart and circulatory physiology Year 2011 Date Published 1/1/2011 Volume : Pages 300 : H374 - H381 PubMed Reference Abstract Ablating insulin receptors in cardiomyocytes causes subendocardial fibrosis and left ventricular (LV) dysfunction after 4 wk of transverse aortic constriction (TAC). To determine whether these maladaptive responses are precipitated by coronary vascular dysfunction, we studied mice with cardiomyocyte-restricted knock out of insulin receptors (CIRKO) and wild-type (WT) TAC mice before the onset of overt LV dysfunction. Two weeks of TAC produced comparable increases (P < 0.05 vs. respective sham) in heart weight/body weight (mg/g) in WT-TAC (8.03 卤 1.14, P < 0.05 vs. respective sham) and CIRKO-TAC (7.76 卤 1.25, P < 0.05 vs. respective sham) vs. WT-sham (5.64 卤 0.11) and CIRKO-sham (4.64 卤 0.10) mice. In addition, 2 wk of TAC were associated with similar LV geometry and function (echocardiography) and interstitial fibrosis (picrosirius red staining) in CIRKO and WT mice. Responses to acetylcholine (ACh), N(G)-monomethyl-L-arginine (l-NMMA), and sodium nitroprusside (SNP) were measured in coronary arteries that were precontracted to achieve ~70% of maximal tension development using the thromboxane A(2) receptor mimetic U-46619 (~3 脳 10(-6) M). ACh-evoked vasorelaxation was absent in WT-TAC but was present in CIRKO-TAC albeit reduced relative to sham-operated animals. l-NMMA-evoked tension development was similar in vessels from CIRKO-TAC mice but was lower (P < 0.05) in WT-TAC animals vs. the respective sham-operated groups, and SNP-evoked vasorelaxation was similar among all mice. Thus estimates of stimulated and basal endothelial nitric oxide release were better preserved in CIRKO vs. WT mice in response to 2 wk of TAC. These findings indicate that maladaptive LV remodeling previously observed in CIRKO-TAC mice is not precipitated by coronary artery dysfunction, because CIRKO mice exhibit compensatory mechanisms (e.g., increased eNOS transcript and protein) to maintain coronary endothelial function in the setting of pressure overload.

Investigators with authorship
Name Institution E. Dale Abel University of Iowa

Complications
All ComplicationsBioinformatics BoneCardiomyopathy CardiovascularGastro-Intestinal (GI) NephropathyNeuropathy & Neurocognition Pediatric Endocrinology Retinopathy UropathyWound Healing