Metabolic Interventions to Prevent Hypertrophy-Induced Alterations in Contractile Properties In Vitro.

(1) Background: The exact mechanism(s) underlying pathological changes in a heart in transition to hypertrophy and failure are not yet fully understood. However, alterations in cardiac energy metabolism seem to be an important contributor. We characterized an in vitro model of adrenergic stimulation-induced cardiac hypertrophy for studying metabolic, structural, and functional changes over time.

Comparison of human and rodent cell models to study myocardial lipid-induced insulin resistance.

Isolated or cultured cells have proven to be valuable model systems to investigate cellular (patho)biology and for screening of the efficacy of drugs or their possible side-effects. Pluripotent stem cells (PSC) can be readily obtained from healthy individuals as well as from diseased patients, and protocols have been developed to differentiate these cells into cardiomyocytes. Hence, these cellular models are moving center stage for a broader application.

Pivotal role of membrane substrate transporters on the metabolic alterations in the pressure-overloaded heart.

Cardiac pressure overload (PO), such as caused by aortic stenosis and systemic hypertension, commonly results in cardiac hypertrophy and may lead to the development of heart failure. PO-induced heart failure is among the leading causes of death worldwide, but its pathological origin remains poorly understood. Metabolic alterations are proposed to be an important contributor to PO-induced cardiac hypertrophy and failure.

Human embryonic stem cell-derived cardiomyocytes as an in vitro model to study cardiac insulin resistance.

Patients with type 2 diabetes (T2D) and/or insulin resistance (IR) have an increased risk for the development of heart failure (HF). Evidence indicates that this increased risk is linked to an altered cardiac substrate preference of the insulin resistant heart, which shifts from a balanced utilization of glucose and long-chain fatty acids (FAs) towards an almost complete reliance on FAs as main fuel source. This shift leads to a loss of endosomal proton pump activity and increased cardiac fat accumulation, which eventually triggers cardiac dysfunction.

Diabetic db/db mice do not develop heart failure upon pressure overload: a longitudinal in vivo PET, MRI, and MRS study on cardiac metabolic, structural, and functional adaptations.

Aims: Heart failure is associated with altered myocardial substrate metabolism and impaired cardiac energetics. Comorbidities like diabetes may influence the metabolic adaptations during heart failure development. We quantified to what extent changes in substrate preference, lipid accumulation, and energy status predict the longitudinal development of hypertrophy and failure in the non-diabetic and the diabetic heart.

Adipokine Imbalance in the Pericardial Cavity of Cardiac and Vascular Disease Patients.

Aim: Obesity and especially hypertrophy of epicardial adipose tissue accelerate coronary atherogenesis. We aimed at comparing levels of inflammatory and atherogenic hormones from adipose tissue in the pericardial fluid and circulation of cardiovascular disease patients.

Methods And Results: Venous plasma (P) and pericardial fluid (PF) were obtained from elective cardiothoracic surgery patients (n = 37).