Cardiac CD47 drives left ventricular heart failure through Ca2+-CaMKII-regulated induction of HDAC3.

ABSTRACT:

Background

Left ventricular heart failure (LVHF) remains progressive and fatal and is a formidable health problem because ever-larger numbers of people are diagnosed with this disease. Therapeutics, while relieving symptoms and extending life in some cases, cannot resolve this process and transplant remains the option of last resort for many. Our team has described a widely expressed cell surface receptor (CD47) that is activated by its high-affinity secreted ligand, thrombospondin 1 (TSP1), in acute injury and chronic disease; however, a role for activated CD47 in LVHF has not previously been proposed.

Methods and results

In experimental LVHF TSP1-CD47 signaling is increased concurrent with up-regulation of cardiac histone deacetylase 3 (HDAC3). Mice mutated to lack CD47 di

SUBMITTER: Sharifi-Sanjani M 

PROVIDER: S-EPMC4309049 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature