Dipeptidyl Peptidase-4 Regulation of SDF-1/CXCR4 Axis: Implications for Cardiovascular Disease

Jixin Zhong, Sanjay Rajagopalan, Jixin Zhong, Sanjay Rajagopalan

Abstract

Dipeptidyl peptidase-4 (DPP4) is a ubiquitously expressed protease that regulates diverse number of physiological functions. As a dipeptidase, it exerts its catalytic effects on proteins/peptides with proline, alanine, or serine in the penultimate (P1) amino acid residue from the amino terminus. The evidence to date supports an important effect of DPP4 in catalytic cleavage of incretin peptides and this perhaps represents the main mechanism by which DPP4 inhibition improves glycemic control. DPP4 also plays an important role in the degradation of multiple chemokines of which stromal cell-derived factor-1 (SDF-1, also known as CXCL12) is perhaps an increasingly recognized target, given its importance in processes, such as hematopoiesis, angiogenesis, and stem cell homing. In the current review, we will summarize the importance of DPP4-mediated enzymatic processing of cytokines/chemokines with an emphasis on SDF-1 and resultant implications for cardiovascular physiology and disease.

Keywords: CXCR4; SDF-1; cardiovascular; chemokine; dipeptidyl peptidase-4.

Figures

Figure 1
Figure 1
Dipeptidyl peptidase-4 inhibition in modulation of SDF-1 and myocardial angiogenesis: expression of DPP4 increases in myocardial infarction. Suppression of DPP4 enzymatic activities by pharmacological inhibitors preserves SDF-1, which results in an enhanced homing of CXCR4+ progenitor cells from bone marrow to infarcted tissues. CXCR4, chemokine (C–X–C motif) receptor 4; DPP4i, DPP4 inhibitor; MI, myocardial infarction; SDF-1, stromal-derived factor-1.

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