Mechanical load‐dependent cardiac ER stress in vitro and in vivo: Effects of preload and afterload

Abstract

a b s t r a c tProteins are folded in the endoplasmic reticulum (ER). ER stress initially leads to compensatory upregulation of ER chaperones and later to apoptosis, but the contribution of biomechanical load vs. neurohumoral stress to myocardial ER stress is unknown. We show that the ER chaperones Grp78 and calreticulin (CRT) are upregulated by afterload, but not by preload in vitro and in vivo. Angiotensin II upregulated ER chaperones in unloaded muscle strips, but the angiotensin receptor-1 antagonist irbesartan did not significantly blunt the induction of ER chaperones by afterload. In monocrotaline-treated rats, Grp78 and CRT were upregulated in the afterloaded right ventricle, but not in the only neurohumorally stressed left ventricle. These findings suggest that afterload but not preload induces myocardial ER stress, largely independent of angiotensin II signaling.

Tissue-Engineering for the Study of Cardiac Biomechanics

“…Indeed, combined studies using both in vitro and animal models are increasingly common and leverage the relative strengths of each system. For instance, a recent study looking at the different effects of increased preload and afterload on the endoplasmic reticulum (ER) of cardiomyocytes used in vitro and in vivo models to dissect out the effects of mechanical loading from those of purely neurohumoral conditioning, showing that afterload, but not preload, induces myocardial ER stress independently of angiotensin II signaling [100].…”