[Feb. 14] 105th IRCMS Seminar

January 15 2024

We would like to inform you that the 105th IRCMS seminar has been scheduled as below.
* This IRCMS seminar is open to everyone.

Date      : February 14, 2024 (Wednesday)

Time      : 16:00-17:00

ZOOM　: Meeting ID: 879 9397 1725
            　 Passcode: Semsem214

Speaker : Dr. Yoshito Yamashiro (National Cerebral and Cardiovascular Center)

Title        : ECM-mediated Vessel Wall Remodeling

Abstract :

The extracellular matrix (ECM) plays a role in activating intracellular signaling through ECM-cell interactions. How does the ECM work in response to mechanical stress? and how do these changes in the extracellular environment and vascular wall remodeling mechanisms work in tandem to maintain vascular wall homeostasis? are still poorly understood. In our laboratory, we identified the matricellular protein thrombospondin-1 (Thbs1) as an ECM responsible for the mechanical stress in aortic aneurysms (Yamashiro. Sci. Signal., 2015, Yamashiro. Circ. Res. 2018). Furthermore, Thbs1 secreted upon stretch stimulation regulates nuclear translocation of Yes-associated protein (YAP) via cell adhesion motif integrin avß1 (Yamashiro. PNAS, 2020) In Thbs1-deficient mice, Thbs1/ integrin avß1/YAP signaling is inhibited, resulting in maladaptive remodeling of the aorta in response to pressure loading, causing aortic divergence and contributing to neointimal proliferation during carotid artery ligation. Recent findings have demonstrated that neointimal cells causing vascular stenosis originate from endothelial cells (ECs) and that partial endothelial-mesenchymal transition (Partial EndMT) is involved in its molecular mechanism (Yamashiro. Cardiovasc. Res., 2022). In this presentation, I will present the latest findings on the function of the ECM in vascular wall homeostasis and the EndMT mechanism by which ECs differentiate into smooth muscle-like cells, and discuss how cells recognize their intracellular and extracellular environments and regulate the multicellular system.

1. Yamashiro Y, Ramirez K, Nagayama K, Hattori N, Liu Y, Matsunaga S, Tomita S, Kubota Y and Yanagisawa H. Partial endothelial-to-mesenchymal transition (EndMT) mediated by HIF-induced CD45 in neointima formation upon carotid artery ligation. Cardiovasc. Res., Jul 4;119(7):1606-1618, 2023.
2. Yamashiro Y, Thang BQ, Ramirez K, Shin SJ, Kohata T, Ohata S, Nguyen TAV, Ohtsuki S, Nagayama K, Yanagisawa H. Matrix mechanotransduction mediated by thrombospondin-1/integrin/YAP in the vascular remodeling. Proc. Natl. Acad. Sci. USA. 117(18):9896-9905, 2020.
3. Yamashiro Y, Thang BQ, Shin SJ, Lino CA, Nakamura T, Kim J, Sugiyama K, Tokunaga C, Sakamoto H, Osaka M, Davis EC, Wagenseil JE, Hiramatsu Y, Yanagisawa H. Role of thrombospondin-1 in mechanotransduction and development of thoracic aortic aneurysm in mouse and humans. Circ. Res. 123(6):660-672, 2018.

Flyer: (Click to enlarge)