Myocardial Myocyte Remodeling and Fibrosis in the Cardiometabolic Syndrome

Abstract

Myocardial cellular and extracellular matrix remodeling are important in the development of left ventricular hypertrophy and are essential for the adaptive and maladaptive changes associated with the cardiometabolic syndrome. This brief review of myocyte remodeling also presents preliminary observational findings regarding myocardial adaptive hypertrophy remodeling, including an increase in mitochondria and capillaries, convolutions and lengthening of intercalated discs, the addition of sarcomeres, thickened Z lines, and the novel presence of pericapillary fibrosis (in addition to perivascular arteriolar fibrosis). The 11-week-old TG(mREN-2)27 transgene rat model of tissue angiotensin II overexpression, which develops hypertension and insulin resistance, was chosen to examine both myocyte hypertrophy and extracellular matrix fibrosis. This review and the preliminary observational findings may provide the clinician and researcher a better understanding of remodeling changes in the myocardium and ultimately foster earlier recognition and therapeutic interventions.

Hyperglycemia aggravates atrial interstitial fibrosis, ionic remodeling and vulnerability to atrial fibrillation in diabetic rabbits

“…The pathophysiology of diabetic cardiomyopathy is multifactorial, and major reason has been attributed to persistent hyperglycemia (11). Hayden et al (12) showed that high glucose levels have been shown to induce myocardial fibrosis in rats.…”

Ultrastructure Study of Transgenic Ren2 Rat Aorta – Part 1: Endothelium and Intima

“…The male transgenic heterozygous (mRen2)27 (Ren2) rat overexpresses the mouse renin gene and is known to have increased local tissue levels of angiotensin II (Ang II), low plasma renin activity and increased plasma levels of aldosterone [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15]. Transgenic Ren2 rats manifest an activated renin-angiotensin-aldosterone system (RAAS) and altered autonomic nervous system regulation [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15].…”

Possible Mechanisms of Local Tissue Renin-Angiotensin System Activation in the Cardiorenal Metabolic Syndrome and Type 2 Diabetes Mellitus

“…By limiting our discussion to these particular end-organs, we did not go into any in-depth discussion of the cardiovascular system, retina, neuronal systems (brain or peripheral neuronal unit), kidney or ovary. The following references may be helpful to those who wish to learn more about those end-organ systems that were not included in this discussion [30,39,40,109,110,111,112,113,114,115,116,117]. …”

“…Further, this mechanism may be responsible for the early findings of pericapillary and perivascular fibrosis in the Ren2 model of hypertension and insulin resistance, which manifests tissue overexpression of the mouse renin gene [37,38,39,40]. …”

“…Hyperglycemia-glucotoxicity is a commonly known environment responsible for the production of ROS and activation of the ROS-tRAS axis [30,36,37,38,39,40,41,42,43,44,45,46]. This environment generates ROS largely by glucose autoxidation and the generation of glycated proteins, including advanced glycation end-products (AGE) and RAGE (their receptor), which increase ROS and inactivate and/or deplete essential antioxidant enzymes such as superoxide dismutase, catalase, and uncoupling of the eNOS enzyme [30,37,41].…”