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Role of Endothelial TRPC3 Channels in Endoplasmic Reticulum Stress Induced Apoptosis in Human Coronary Endothelial Cells
Author(s) -
Smedlund Kathryn,
Ingels Marcel,
Vazquez Guillermo
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.876.6
Subject(s) - trpc3 , unfolded protein response , endoplasmic reticulum , thapsigargin , apoptosis , microbiology and biotechnology , biology , cancer research , endothelial stem cell , signal transduction , endocrinology , medicine , receptor , transient receptor potential channel , trpc , biochemistry , in vitro
Atherosclerosis is a chronic inflammatory disease of the arterial wall and represents the major cause of coronary artery disease. The balance between apoptosis and survival signaling pathways is crucial to maintaining endothelial integrity during vascular injury, and alteration of these processes has been associated to atherogenesis. Endoplasmic reticulum (ER) stress has emerged as a critical player in development of atherosclerotic lesions. Despite its beneficial and essential corrective functions, chronic ER stress, through persistent activation of the unfolded protein response (UPR) can alter the balance between apoptosis and survival favoring lesion progression. In recent studies, we found that in human coronary artery endothelial cells (HCAECs) Transient Receptor Potential Canonical 3 (TRPC3), a member of the larger TRP superfamily of channel forming proteins, plays a role in cell survival and apoptosis. In HCAECs knockdown of TRPC3 results in an increase in the number of apoptotic cells in response to the ER stressor thapsigargin. This correlated positively with increased expression of typical ER stress markers such as CHOP and BiP. Altogether, this data suggests that TRPC3 expression and function may have a protective role in HCAECs and that TRPC3 deficiency and/or deregulation may sensitize HCAECs to the pro‐apoptotic actions of sustained ER stress. Research support: AHA 12POST11910042 to KS, R01HL111877–01 to GV.