Cardiac Sympathetic Denervation Mitigated Ischemic Cardiomyopathy Progression in a Rat Model of Sleep Apnea.

Background: Ischemic cardiomyopathy with comorbid obstructive sleep apnea syndrome is associated with worse long-term outcomes. Intermittent hypoxia (IH), a key feature of obstructive sleep apnea, exacerbates sympathetic activity, hastening cardiac dysfunction and remodeling in ischemic cardiomyopathy rat models. This study explores whether targeted cardiac sympathetic denervation (CSD) can limit IH-induced progression of ischemic cardiomyopathy.

Signaling through cAMP-Epac1 induces metabolic reprogramming to protect podocytes in glomerulonephritis.

Unlike classical protein kinase A, with separate catalytic and regulatory subunits, EPACs are single chain multi-domain proteins containing both catalytic and regulatory elements. The importance of cAMP-Epac-signaling as an energy provider has emerged over the last years. However, little is known about Epac1 signaling in chronic kidney disease.

Macromolecular Complex Including MLL3, Carabin and Calcineurin Regulates Cardiac Remodeling.

Background: Cardiac hypertrophy is an intermediate stage in the development of heart failure. The structural and functional processes occurring in cardiac hypertrophy include extensive gene reprogramming, which is dependent on epigenetic regulation and chromatin remodeling. However, the chromatin remodelers and their regulatory functions involved in the pathogenesis of cardiac hypertrophy are not well characterized.

Inhalation of acidic nanoparticles prevents doxorubicin cardiotoxicity through improvement of lysosomal function.

Doxorubicin (Dox) is an effective anticancer molecule, but its clinical efficacy is limited by strong cardiotoxic side effects. Lysosomal dysfunction has recently been proposed as a new mechanism of Dox-induced cardiomyopathy. However, to date, there is a paucity of therapeutic approaches capable of restoring lysosomal acidification and function in the heart.

Diabetic cardiomyopathy: the need for adjusting experimental models to meet clinical reality.

Diabetic cardiomyopathy (CM), occurring in the absence of hypertension, coronary artery disease, and valvular or congenital heart disease, is now recognized as a distinct, multifactorial disease leading to ventricular hypertrophy and abnormal myocardial contractility that correlates with an array of complex molecular and cellular changes. Animal models provide the unique opportunity to investigate mechanistic aspects of diabetic CM, but important caveats exist when extrapolating findings obtained from preclinical models of diabetes to humans. Indeed, animal models do not recapitulate the complexity of environmental factors, most notably the duration of the exposure to insulin resistance that may play a crucial role in the development of diabetic CM.

Short-term intermittent hypoxia induces simultaneous systemic insulin resistance and higher cardiac contractility in lean mice.

Background: Intermittent hypoxia (IH) is the major feature of obstructive sleep apnea syndrome, well-known to induce cardiometabolic complications. We previously demonstrated that IH induces hyperinsulinemia and associated altered insulin signaling in adipose tissue, liver, and skeletal muscle, but impact of IH on cardiac insulin signaling and functional/structural consequences remains unknown. Therefore, the aims of this study were to investigate in both lean and obese mice the effects of chronic IH on the following: (1) cardiac insulin signaling and (2) cardiac remodeling and function.

Intermittent Hypoxia Triggers Early Cardiac Remodeling and Contractile Dysfunction in the Time-Course of Ischemic Cardiomyopathy in Rats.

BACKGROUND Sleep-disordered breathing is associated with a poor prognosis (mortality) in patients with ischemic cardiomyopathy. The understanding of mechanisms linking intermittent hypoxia (IH), the key feature of sleep-disordered breathing, to ischemic cardiomyopathy progression is crucial for identifying specific actionable therapeutic targets. The aims of the present study were (1) to evaluate the impact of IH on the time course evolution of cardiac remodeling and contractile dysfunction in a rat model of ischemic cardiomyopathy; and (2) to determine the impact of IH on sympathetic activity, hypoxia inducible factor-1 activation, and endoplasmic reticulum stress in the time course of ischemic cardiomyopathy progression.