Electrophysiological Mechanisms of Ventricular Fibrillation Induction

Ventricular fibrillation (VF) is known as a main responsible cause of sudden cardiac death which claims thousands of lives each year. Although the mechanism of VF induction has been investigated for over a century, its definite mechanism is still unclear. In the past few decades, the development of new advance technologies has helped investigators to understand how the strong stimulus or the shock induces VF. New hypotheses have been proposed to explain the mechanism of VF induction. This article reviews most commonly proposed hypotheses that are believed to be the mechanism of VF induction

Links Between Obesity-Induced Brain Insulin Resistance, Brain Mitochondrial Dysfunction, and Dementia

It is widely recognized that obesity and associated metabolic changes are considered a risk factor to age-associated cognitive decline. Inflammation and increased oxidative stress in peripheral areas, following obesity, are patently the major contributory factors to the degree of the severity of brain insulin resistance as well as the progression of cognitive impairment in the obese condition. Numerous studies have demonstrated that the alterations in brain mitochondria, including both functional and morphological changes, occurred following obesity. Several studies also suggested that brain mitochondrial dysfunction may be one of underlying mechanism contributing to brain insulin resistance and cognitive impairment in the obese condition. Thus, this review aimed to comprehensively summarize and discuss the current evidence from various in vitro, in vivo, and clinical studies that are associated with obesity, brain insulin resistance, brain mitochondrial dysfunction, and cognition. Contradictory findings and the mechanistic insights about the roles of obesity, brain insulin resistance, and brain mitochondrial dysfunction on cognition are also presented and discussed. In addition, the potential therapies for obese-insulin resistance are reported as the therapeutic strategies which exert the neuroprotective effects in the obese-insulin resistant condition

Mitochondrial Link Between Metabolic Syndrome and Pre-Alzheimer’s Disease

There is much evidence to demonstrate that the presence of the metabolic syndrome (MetS) is associated with an increase in the incidence of pre-Alzheimer’s disease. The possible underlying mechanisms linking pre-Alzheimer’s disease and MetS are still unclear. This study summarizes and discusses the potential mechanisms involved in pre-Alzheimer’s disease under MetS conditions, including an increased brain oxidative stress, brain inflammation, brain mitochondrial dysfunction, hyper-phosphorylated tau protein, and amyloid beta production. This report focuses on brain mitochondrial alterations in cases of pre-Alzheimer’s disease where MetS is also extant. The data from in vitro, in vivo, and clinical studies are included. In addition, potential interventions against pre-Alzheimer’s disease in conjunction with MetS are summarized and discussed

Cellular Electrophysiology of Iron-Overloaded Cardiomyocytes

Iron, the most abundant transition metal element in the human body, plays an essential role in many physiological processes. However, without a physiologically active excretory pathway, iron is subject to strict homeostatic processes acting upon its absorption, storage, mobilization, and utilization. These intricate controls are perturbed in primary and secondary hemochromatoses, leading to a deposition of excess iron in multiple vital organs including the heart. Iron overload cardiomyopathy is the leading cause of mortality in patients with iron overload conditions. Apart from mechanical deterioration of the siderotic myocardium, arrhythmias reportedly contribute to a substantial portion of cardiac death associated with iron overload. Despite this significant impact, the cellular mechanisms of electrical disturbances in an iron-overloaded heart are still incompletely characterized. This review article focuses on cellular electrophysiological studies that directly investigate the effects of iron overload on the function of cardiac ion channels, including trans-sarcolemmal and sarcoplasmic reticulum Ca2+ fluxes, as well as cardiac action potential morphology. Our ultimate aim is to provide a comprehensive summary of the currently available information that will encourage and facilitate further mechanistic elucidation of iron-induced pathoelectrophysiological changes in the heart

Potential mechanisms responsible for cardioprotective effects of sodium–glucose co-transporter 2 inhibitors

Abstract Diabetes mellitus currently affects over 350 million patients worldwide and is associated with many deaths from cardiovascular complications. Sodium–glucose co-transporter 2 (SGLT-2) inhibitors are a novel class of antidiabetic drugs with cardiovascular benefits beyond other antidiabetic drugs. In the EMPA-REG OUTCOME trial, empagliflozin significantly decreases the mortality rate from cardiovascular causes [38% relative risk reduction (RRR)], the mortality rate from all-causes (32% RRR) and the rate of heart failure hospitalization (35% RRR) in diabetic patients with established cardiovascular diseases. The possible mechanisms of SGLT-2 inhibitors are proposed to be systemic effects by hemodynamic and metabolic actions. However, the direct mechanisms are not fully understood. In this review, reports concerning the effects of SGLT-2 inhibitors in models of diabetic cardiomyopathy, heart failure and myocardial ischemia from in vitro, in vivo as well as clinical reports are comprehensively summarized and discussed. By current evidences, it may be concluded that the direct effects of SGLT-2 inhibitors are potentially mediated through their ability to reduce cardiac inflammation, oxidative stress, apoptosis, mitochondrial dysfunction and ionic dyshomeostasis

Recent Advances in Mitochondrial Fission/Fusion-Targeted Therapy in Doxorubicin-Induced Cardiotoxicity

Doxorubicin (DOX) has been recognized as one of the most effective chemotherapies and extensively used in the clinical settings of human cancer. However, DOX-mediated cardiotoxicity is known to compromise the clinical effectiveness of chemotherapy, resulting in cardiomyopathy and heart failure. Recently, accumulation of dysfunctional mitochondria via alteration of the mitochondrial fission/fusion dynamic processes has been identified as a potential mechanism underlying DOX cardiotoxicity. DOX-induced excessive fission in conjunction with impaired fusion could severely promote mitochondrial fragmentation and cardiomyocyte death, while modulation of mitochondrial dynamic proteins using either fission inhibitors (e.g., Mdivi-1) or fusion promoters (e.g., M1) can provide cardioprotection against DOX-induced cardiotoxicity. In this review, we focus particularly on the roles of mitochondrial dynamic pathways and the current advanced therapies in mitochondrial dynamics-targeted anti-cardiotoxicity of DOX. This review summarizes all the novel insights into the development of anti-cardiotoxic effects of DOX via the targeting of mitochondrial dynamic pathways, thereby encouraging and guiding future clinical investigations to focus on the potential application of mitochondrial dynamic modulators in the setting of DOX-induced cardiotoxicity

Current evidence regarding the cellular mechanisms associated with cancer progression due to cardiovascular diseases

Abstract Several large cohort studies in cardiovascular disease (CVD) patients have shown an increased incidence of cancer. Previous studies in a myocardial infarction (MI) mouse model reported increased colon, breast, and lung cancer growth. The potential mechanisms could be due to secreted cardiokines and micro-RNAs from pathological hearts and immune cell reprogramming. A study in a MI-induced heart failure (HF) mouse demonstrated an increase in cardiac expression of SerpinA3, resulting in an enhanced proliferation of colon cancer cells. In MI-induced HF mice with lung cancer, the attenuation of tumor sensitivity to ferroptosis via the secretion of miR-22-3p from cardiomyocytes was demonstrated. In MI mice with breast cancer, immune cell reprogramming toward the immunosuppressive state was shown. However, a study in mice with renal cancer reported no impact of MI on tumor growth. In addition to MI, cardiac hypertrophy was shown to promote the growth of breast and lung cancer. The cardiokine potentially involved, periostin, was increased in the cardiac tissue and serum of a cardiac hypertrophy model, and was reported to increase breast cancer cell proliferation. Since the concept that CVD could influence the initiation and progression of several types of cancer is quite new and challenging regarding future therapeutic and preventive strategies, further studies are needed to elucidate the potential underlying mechanisms which will enable more effective risk stratification and development of potential therapeutic interventions to prevent cancer in CVD patients