High-density lipoprotein infusion therapy for heart failure with reduced ejection fraction and heart failure with preserved ejection fraction.
Heart failure (HF) is a growing public health problem, the leading cause of hospitalization, and a major cause of mortality. Approximately 50% of chronic HF patients have HF with reduced ejection fraction (HFrEF) and 50% suffer from HF with preserved ejection fraction (HFpEF). As the population ages, HFpEF will continue to be a growing public health problem. In contrast to advances in the treatment of patients with HFrEF, drug strategies with strong evidence in HFrEF have proved unsuccessful in HFpEF and the mortality in patients with HFpEF has remained unchanged. Plasma high-density lipoprotein (HDL) cholesterol levels and levels of its major apolipoprotein (apo), apo A-I, are inversely correlated with the incidence of coronary heart disease. HDLs exert divergent functions that include actions mediated by signalling via scavenger receptor class B, type I (SR-BI), and/or receptor activation by HDL cargo molecules. These pleiotropic properties offer perspectives for new therapeutic areas for HDL-targeted interventions. The general objective of this project is to study the effect of administration of apo A-I Milano/phospholipid complexes (HDL Milano)in a murine model of established HFrEF and in murine models with established HFpEF. Specific mechanisms of action of this therapy will be elucidated. The feasibility of the project is supported by substantial preliminary results showing beneficial effects of HDL Milano administration on cardiac structure and function in one model.