title: Mechanical load-dependent cardiac ER stress in vitro and in vivo: effects of preload and afterload.
abstract: 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.
authors.affiliation: Department of Cardiology and Pneumology, Georg-August-University, Goettingen, Germany. ktoischer@med.uni-goettingen.de
authors.forename: Karl
authors.initials: K
authors.lastname: Toischer
authors.forename: Simon
authors.initials: S
authors.lastname: Kochhäuser
authors.forename: Phuc
authors.initials: P
authors.lastname: Nguyen van
authors.forename: Kirsten
authors.initials: K
authors.lastname: Leineweber
authors.forename: Gerd
authors.initials: G
authors.lastname: Hasenfuss
authors.forename: Harald
authors.initials: H
authors.lastname: Kögler
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001696:Biomechanical Phenomena; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005260:Female; D008297:Male; D051379:Mice; D016686:Monocrotaline / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D011312:Pressure; D011817:Rabbits; D051381:Rats; D013314:Stress, Mechanical; D013997:Time Factors
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717248:Hspa5 protein, mouse; D000804:Angiotensin II; D016686:Monocrotaline