Mechanical stretch‐induced endoplasmic reticulum stress, apoptosis and inflammation contribute to thoracic aortic aneurysm and dissection

Abstract

Thoracic aortic aneurysm/dissection (TAAD) is characterized by excessive smooth muscle cell (SMC) loss, extracellular matrix (ECM) degradation and inflammation. In response to certain stimuli, endoplasmic reticulum (ER) stress is activated and regulates apoptosis and inflammation. Excessive apoptosis promotes aortic inflammation and degeneration, leading to TAAD. Therefore, we studied the role of ER stress in TAAD formation. A lysyl oxidase inhibitor, 3‐aminopropionitrile fumarate (BAPN), was administrated to induce TAAD formation in mice, which showed significant SMC loss (α‐SMA level). Excessive apoptosis (TUNEL staining) and ER stress (ATF4 and CHOP), along with inflammation, were present in TAAD samples from both mouse and human. Transcriptional profiling of SMCs after mechanical stress demonstrated the expression of genes for ER stress and inflammation. To explore the causal role of ER stress in initiating degenerative signalling events and TAAD, we treated wild‐type (CHOP +/+) or CHOP −/− mice with BAPN and found that CHOP deficiency protected against TAAD formation and rupture, as well as reduction in α‐SMA level. Both SMC apoptosis and inflammation were significantly reduced in CHOP −/− mice. Moreover, SMCs isolated from CHOP −/− mice were resistant to mechanical stress‐induced apoptosis. Taken together, our results demonstrated that mechanical stress‐induced ER stress promotes SMCs apoptosis, inflammation and degeneration, providing insight into TAAD formation and progression. © 2015 Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Macrophage-Derived mir-155-Containing Exosomes Suppress Fibroblast Proliferation and Promote Fibroblast Inflammation during Cardiac Injury

“…46 Heart tissues were fixed in 4% paraformaldehyde, embedded in paraffin, and sectioned (5 mm). Heart sections were incubated with antibodies against BrdU, collagen I (1:500), and a-SMA (1:200) at 4 C overnight, then with secondary antibodies at room temperature for 30 min and detected with 3,3 0 -diaminobenzidine for immunohistochemistry.…”

Toll-like receptor-4 signaling pathway in aorta aging and diseases: “its double nature”

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Cyclic Mechanical Stretch Induced Smooth Muscle Cell Changes in Cerebral Aneurysm Progress by Reducing Collagen Type IV and Collagen Type VI Levels

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