Diabetic Cardiomyopathy Metabolic disorders are major risk factors for diabetes, and cardiovascular diseases that result from high-calorie intake and minimal physical activity (Noda et al. 2014). “Obesity, insulin resistance, hypertension, glucose intolerance, and hyperlipidemia” are common characteristics of these disorders (Noda et al. 2014). Past research has found that ROCKs are activated in metabolic disorders. Recently, inhibiting Rho-kinase activity with fasudil has been linked to the improvement of high-fat diet-induced metabolic conditions via the activation of the AMP-activated kinase (AMPK) pathway in murine models. AMPK is a heterotrimeric enzyme that has been found to increase oxygen consumption, glucose metabolism, and fatty…show more content… 2015). Diabetes is characterized by the body’s inability to produce adequate amounts of insulin, which causes elevated levels of glucose in the blood, a condition referred to as hyperglycemia. Diabetes will eventually progress into diabetic cardiomyopathy, which is associated with myocardial dysfunction, independent of coronary vascular disease, and hypertension (Waddingham et al. 2015; Zhou et al. 2011). General characteristics of diabetic cardiomyopathy include left ventricular diastolic dysfunction, cardiac fibrosis, and cardiomyocyte hypertrophy (Waddingham et al. 2015; Zhou et al. 2011). Left ventricular diastolic dysfunction begins in the early stages of diabetes, and it’s thought to be induced by various intracellular modifications in cardiomyocytes such as, defective Ca2+-handling abilities, a reduction in ATPase activity, and sarcomeric dysfunction (Waddingham et al.…show more content… This is mainly the result of an overabundance of collagen found within the interstitial spaces of the cardiac muscle, which has been found to result in diastolic and systolic dysfunction (Zhou et al. 2011). A general pathological response to tissue damage is the development of fibrosis, which is involved in the proliferation of cardiac fibroblasts. Cardiac fibroblasts are responsible for collagen synthesis and growth factor secretion aiding in the conservation of myocardial function. However, sustained activation of cardiac fibroblasts leads to another major pathological process of diabetic cardiomyopathy referred to as cardiac fibrosis (Zhou et al. 2011). ROCK isoforms 1 and 2 have been linked to the pathogenesis of cardiac fibrosis and cardiac hypertrophy, respectively (Zhou et al. 2011). Through experimental research, Zhou et al. discovered that ROCK activation is vital for high extracellular glucose-induced c-Jun N-terminus kinase (JNK) pathway activation, and the propagation of cardiac fibroblasts and collagen synthesis (2011). The inhibition of ROCK activity has been shown to prevent the pathophysiological changes in cells that results from ischemic injury (Glyn et al. 2003). These results suggest that it’s possible that the ROCK pathway is involved in nuclear signal transduction through activation of the JNK pathway, which
