Format

Send to

Choose Destination
Pharmacol Ther. 2014 Sep;143(3):305-15. doi: 10.1016/j.pharmthera.2014.03.009. Epub 2014 Apr 1.

Stromal derived factor 1α: a chemokine that delivers a two-pronged defence of the myocardium.

Author information

1
The Hatter Cardiovascular Institute, 67 Chenies Mews, London WC1E 6HX, United Kingdom.

Abstract

Alleviating myocardial injury associated with ST elevation myocardial infarction is central to improving the global burden of coronary heart disease. The chemokine stromal cell-derived factor 1α (SDF-1α) has dual potential benefit in this regard. Firstly, SDF-1α is up-regulated in experimental and clinical studies of acute myocardial infarction (AMI) and regulates stem cell migration to sites of injury. SDF-1α delivery to the myocardium after AMI is associated with improved stem cell homing, angiogenesis, and left ventricular function in animal models, and improvements in heart failure and quality of life in humans. Secondly, SDF-1α may have a role in remote ischaemic conditioning (RIC), the phenomenon whereby non-lethal ischaemia-reperfusion applied to an organ or tissue remote from the heart protects the myocardium from lethal ischaemia-reperfusion injury (IRI). SDF-1α is increased in the serum of rats subjected to RIC and protects against myocardial IRI in ex vivo studies. Despite these potential pleiotropic effects, a limitation of SDF-1α is its short plasma half-life due to cleavage by dipeptidyl peptidase-4 (DPP-4). However, DPP-4 inhibitors increase the half-life of SDF-1α by preventing its degradation and are also protective against lethal IRI. In summary, SDF-1 potentially delivers a 'two-pronged' defence of the myocardium: acutely protecting it from IRI while simultaneously stimulating repair by recruiting stem cells to the site of injury. In this article we examine the evidence for acute and chronic cardioprotective roles of SDF-1α and discuss potential therapeutic manipulations of this mechanism with DPP-4 inhibitors to protect against lethal tissue injury in the clinical setting.

KEYWORDS:

AMI; CXCR4; Cardioprotection; DPP-4; Ischemic conditioning; SDF

PMID:
24704323
PMCID:
PMC4127789
DOI:
10.1016/j.pharmthera.2014.03.009
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center