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Matrix Biol. 2014 Jul;37:92-101. doi: 10.1016/j.matbio.2014.01.002. Epub 2014 Jan 11.

Thrombospondin-1 and CD47 regulation of cardiac, pulmonary and vascular responses in health and disease.

Author information

1
Vascular Medicine Institute, University of Pittsburgh School of Medicine; Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA 15261, United States.
2
Vascular Medicine Institute, University of Pittsburgh School of Medicine.
3
Vascular Medicine Institute, University of Pittsburgh School of Medicine; Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine.
4
Vascular Medicine Institute, University of Pittsburgh School of Medicine; Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine; Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine; Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA 15261, United States. Electronic address: jsi5@pitt.edu.

Abstract

Cardiovascular homeostasis and health is maintained through the balanced interactions of cardiac generated blood flow and cross-talk between the cellular components that comprise blood vessels. Central to this cross-talk is endothelial generated nitric oxide (NO) that stimulates relaxation of the contractile vascular smooth muscle (VSMC) layer of blood vessels. In cardiovascular disease this balanced interaction is disrupted and NO signaling is lost. Work over the last several years indicates that regulation of NO is much more complex than previously believed. It is now apparent that the secreted protein thrombospondin-1 (TSP1), that is upregulated in cardiovascular disease and animal models of the same, on activating cell surface receptor CD47, redundantly inhibits NO production and NO signaling. This inhibitory event has implications for baseline and disease-related responses mediated by NO. Further work has identified that TSP1-CD47 signaling stimulates enzymatic reactive oxygen species (ROS) production to further limit blood flow and promote vascular disease. Herein consideration is given to the most recent discoveries in this regard which identify the TSP1-CD47 axis as a major proximate governor of cardiovascular health.

KEYWORDS:

Blood flow; CD47; Cardiovascular disease; Nitric oxide; ROS; Thrombospondin-1

PMID:
24418252
PMCID:
PMC4096433
DOI:
10.1016/j.matbio.2014.01.002
[Indexed for MEDLINE]
Free PMC Article
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