Inflammation and Diabetic Cardiomyopathy

Diabetes mellitus (DM) is a metabolic syndrome that manifests a low grade of systemic inflammation that contributes to the development of cardiovascular diseases (CVDs). DM is a predominant risk factor for CVDs inducing structural changes in the heart, infiltration of fibrosis, apoptosis, and cardiac remodeling, all leading to myocardial infarction (MI), heart failure (HF), and sudden cardiac death. Furthermore, more than 80% of diabetic patients usually die from heart diseases or diabetic cardiomyopathy (DCM). Currently, HF is one of the main causes of mortality in the world despite advances in drug treatments. According to literature, a strong association exists between chronic inflammation and the development of DCM. In order to have a better appreciation of the effect of diabetes and inflammation on the cardiovascular system (CVS), it is of paramount importance to have a better understanding of diabetes, the physiology of the CVS, and the pathophysiology of DM. Thus, the present review highlights the role of chronic inflammation in the complex interplay between the development of DM and DCM. Our understanding of the process is critical in the discovery of new targeted therapies for DCM and other forms of HF

Contraction and Intracellular Calcium Transport in Epicardial and Endocardial Ventricular Myocytes from Streptozotocin-Induced Diabetic Rat

Diabetes mellitus (DM) is a global health problem. According to the International Diabetes Federation, 424.9 million people suffered from DM in 2017 and this number is expected to rise to 628.6 million by 2045. Although diabetes can affect every organ in the body, cardiovascular disease is a major cause of death and disability in people with diabetes. Diabetic patients frequently suffer from systolic and diastolic dysfunction. Within the ventricles, the electromechanical properties of cardiac myocytes vary transmurally. The aim of this study was to investigate contraction and Ca2+ transport in epicardial (EPI) and endocardial (ENDO) myocytes from the left ventricle in the streptozotocin (STZ)-induced diabetic rat heart. Experiments were performed 5–6 months after STZ treatment. Ventricular myocytes were isolated by enzymic and mechanical dispersal techniques from EPI and ENDO regions of the left ventricle. Contraction and free intracellular Ca2+ concentration (Ca2+)i were measured by video edge detection and fl uorescence photometry techniques, respectively. Myocyte length and calculated surface area were smaller in EPI-STZ compared to EPI-CON. Time to peak (TPK) shortening was prolonged in EPI-STZ compared to EPI-CON and in ENDO-STZ compared to ENDO-CON myocytes. Time to half (THALF) relaxation of shortening was prolonged in EPI-STZ compared to EPI-CON. TPK Ca2+ transient was prolonged in EPI-STZ compared to EPI-CON, ENDO-STZ compared to ENDO-CON, ENDO-STZ compared to EPI-STZ and in ENDO-CON compared to EPI-CON myocytes. THALF decay of the Ca2+ transient was prolonged in ENDO-STZ compared to ENDO-CON. Fractional release of Ca2+ was increased in ENDO-STZ compared to ENDO-CON and in ENDO-STZ compared to EPI-STZ. Recovery of the Ca2+ transient was prolonged in ENDO-STZ compared to ENDO-CON. In conclusion, the kinetics of contraction and Ca2+ transient, fractional release of Ca2+ from the sarcoplasmic reticulum are altered to different extents in EPI and ENDO myocytes from STZ-induced diabetic rat

The Role of Oxidative Stress in the Development of Diabetic Cardiomyopathy

Diabetes mellitus (DM) is a major global health problem, currently affecting about 460 million people while another billion have prediabetes, all costing the governments of the world over $1 trillion USAD to diagnose and treat diabetic patients, so that they can enjoy a better quality of life. DM induces hyperglycemia (HG), which in turn plays a significant role in the development of diabetic cardiomyopathy (DCM), which is responsible for over 80% of diabetic mortality. The exact mechanisms underlying DCM remain incompletely clear, although several pathological mechanisms responsible for DCM have been proposed in the literature. One such mechanism is oxidative stress (OS), which is widely considered as one of the major causes for the pathogenesis of the disease. There is a growing scientific and public interest in connecting oxidative stress with a variety of pathological conditions, including DM as well as other human diseases. HG-induced oxidative stress is a major risk factor for the development of micro-vascular pathogenesis in the diabetic myocardium, resulting in myocardial cell death, hypertrophy, fibrosis, abnormalities of calcium homeostasis and endothelial dysfunction. The aim of this review is to highlight the role of oxidative stress in the development of DCM

Diabetic Cardiomyopathy and the Role of Regular Exercise in Preventing the Disease: A Review

Diabetes mellitus (DM) is a major global metabolic disorder currently affecting over 450 million people and this number is rising rapidly. Heart failure (HF) is the major cause of death among diabetic patients. The disorder is due to elevated blood glucose level beyond physiological range or hyperglycaemia (HG), which in turn leads to a number of long-term complications, including diabetic cardiomyopathy (DC) over time. Around 80% of all diabetics will eventually die from DC. If left untreated, DC has been shown to be a critical factor in HF, independent of atherosclerosis, hypertension and valvular malfunction. The inability to maintain glucose homeostasis in the myocardium compromises cardiac structure and function in human diabetic subjects and also in animals with experimental diabetes. Daily exercise is known to protect the heart from sudden cardiac death. Exercise training (ET) is a beneficial non-pharmacological intervention for the treatment of cardiovascular diseases (CVDs). ET can induce cardio-protection in normal hearts and also in a partially diseased heart through a range of molecular mechanisms. The cardio-protective effect of ET is associated with the improvement of antioxidant capacity, mitochondrial viability and it can activate physiological cardiac growth, which are all mediated via distinct cellular and molecular mechanisms compared to those in pathological hypertrophy. Beneficial cardiac protection following regular ET in diabetes has been reported in both clinical and experimental animal studies. ET is a cost-effective strategy for prevention and treatment DC. However, the cellular and molecular mechanisms underlying DC and HF in diabetes and how regular exercise can reverse the pathology are not fully clear and further research should be carried out

Calcium signaling in endocardial and epicardial ventricular myocytes from streptozotocin‐induced diabetic rats

Aims/Introduction: Abnormalities in Ca2+ signaling have a key role in hemodynamic dysfunction in diabetic heart. The purpose of this study was to explore the effects of streptozotocin (STZ) - induced diabetes on Ca2+ signaling in epicardial (EPI) and endocardial (ENDO) cells of the left ventricle, after 5-6 months of STZ injection. Materials and Methods: Whole-cell patch clamp was used to measure L-type Ca2+ channel (LTCC) and Na+/Ca2+ exchanger (NCX) currents. Fluorescence photometry techniques were used to measure intracellular free Ca2+ concentration [Ca2+]i. Results: Although LTCC current was not significantly altered, the amplitude (AMP) of Ca2+ transients increased significantly in EPI-STZ and ENDO-STZ compared to controls. Time to peak (TPK) LTCC current, TPK Ca2+ transient, time to half (THALF) decay of LTCC current and THALF decay of Ca2+ transients were not significantly changed in EPI-STZ and ENDO-STZ myocytes compared to controls. NCX current was significantly smaller in EPI-STZ and in ENDO-STZ compared to controls. Conclusions: STZ-induced diabetes resulted in an increase in AMP of Ca2+ transients in EPI and ENDO myocyte that was independent of LTCC current. Such an effect can be attributed, at least in part, to the dysfunction of NCX. Additional studies are warranted to improve our understanding of the regional impact of diabetes on Ca2+ signaling, which will facilitate the discovery of new targeted treatments for diabetic cardiomyopathy

Calcium signaling in endocardial and epicardial ventricular myocytes from streptozotocin-induced diabetic rats

© 2020 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd Aims/Introduction: Abnormalities in Ca2+ signaling have a key role in hemodynamic dysfunction in diabetic heart. The purpose of this study was to explore the effects of streptozotocin (STZ)-induced diabetes on Ca2+ signaling in epicardial (EPI) and endocardial (ENDO) cells of the left ventricle after 5–6 months of STZ injection. Materials and Methods: Whole-cell patch clamp was used to measure the L-type Ca2+ channel (LTCC) and Na+/Ca2+ exchanger currents. Fluorescence photometry techniques were used to measure intracellular free Ca2+ concentration. Results: Although the LTCC current was not significantly altered, the amplitude of Ca2+ transients increased significantly in EPI-STZ and ENDO-STZ compared with controls. Time to peak LTCC current, time to peak Ca2+ transient, time to half decay of LTCC current and time to half decay of Ca2+ transients were not significantly changed in EPI-STZ and ENDO-STZ myocytes compared with controls. The Na+/Ca2+ exchanger current was significantly smaller in EPI-STZ and in ENDO-STZ compared with controls. Conclusions: STZ-induced diabetes resulted in an increase in amplitude of Ca2+ transients in EPI and ENDO myocytes that was independent of the LTCC current. Such an effect can be attributed, at least in part, to the dysfunction of the Na+/Ca2+ exchanger. Additional studies are warranted to improve our understanding of the regional impact of diabetes on Ca2+ signaling, which will facilitate the discovery of new targeted treatments for diabetic cardiomyopathy

Mechanisms of Diabetes Mellitus-Induced Sudden Cardiac Death

More than 450 million people worldwide have diabetes mellitus (DM), a metabolic disorder characterized by an increase in blood glucose level (hyperglycemia) that arises from insufficient insulin secretion or resistance to insulin’s action. More than 70% of individuals with chronic DM will develop cardiovascular diseases (CVDs) including atherosclerosis and coronary artery diseases (CADs), hypertension, cardiac arrhythmias, cardiomyopathy (heart failure), stroke, and chronic kidney disease. A significant number of these individuals will also succumb to sudden cardiac death (SCD). SCD usually occurs in early morning from abnormal heart rhythms or arrhythmias and ventricular fibrillation. When the pumping action of the heart becomes erratic, a reduction in oxygenated blood to the brain leads to unconsciousness and brain damage. SCD is independent of age and sex and positively correlates with impairment in cardiac metabolism, muscle damage, fibrosis, apoptosis, hypertrophy, ischemia, and deranged cation signaling. This review centers on mechanisms by which intracellular cations (Na+, K+, and Ca2+) handling, inflammation, and oxidative and carbonyl stresses due to diabetes-induced hyperglycemia can lead to the deterioration of excitation/contraction coupling (ECC), impaired contractility, arrhythmias, and SCD in DM patients. It also discusses the beneficial effects of exercise training to attenuate the risk of SCD