Key result
Afterload, but not preload, upregulated the ER chaperones Grp78 and calreticulin in vitro and in vivo, largely independent of angiotensin II signaling.
Why the study?
Does biomechanical afterload induce myocardial ER stress independent of neurohumoral stress in vitro and in vivo?
Does biomechanical afterload induce myocardial ER stress independent of neurohumoral stress in vitro and in vivo?
Afterload, but not preload, induces myocardial ER stress largely independent of angiotensin II signaling, highlighting a specific biomechanical trigger for ER stress.
Afterload may represent a distinct myocardial ER stress trigger; hypothesis-generating in animal models and leaves open clinical relevance beyond angiotensin II blockade.
Proteins 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.
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Toischer et al. (2012) studied Myocardial ER stress. Afterload vs. Preload was evaluated on Upregulation of ER chaperones Grp78 and calreticulin (CRT). Afterload, but not preload, upregulated the ER chaperones Grp78 and calreticulin in vitro and in vivo, largely independent of angiotensin II signaling.
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