Stromal Cell-derived Factor-1alpha Improves Infarcted Heart Function Through Angiogenesis in Mice

Background: Local delivery of stromal cell-derived factor-1alpha (SDF-1) has been demonstrated to improve hind limb ischemia through enhanced neovascularization in animals. It was hypothesized that local administration of SDF-1 also contributes to neovascularization of ischemic heart.

Method: Acute myocardial infarction was created by left coronary artery ligation in C57BL/6J mice. Immediately after infarction induction, mice were treated by injection directly into the center of ischemic myocardium either with saline (control group) or SDF-1 (SDF-1 group). Cardiac function was measured on echocardiogram 2 and 4 weeks after infarction. On week 4 mice were killed to evaluate infarction size and capillary vessel density. To determine the contribution of bone marrow cells to angiogenesis, the same procedures were performed on C57BL/6J chimeric mice reconstituted with green fluorescent protein-positive bone marrow cells.

Results: Fractional shortening was greater in the SDF-1 group at 4 weeks (0.31 +/- 0.06% vs 0.23 +/- 0.03%, P = 0.037). The infarct area was smaller in the SDF-1 group compared to the control group (9.31 +/- 2.76% vs 18.07 +/- 5.69%, P = 0.028). Green fluorescent protein-positive cells accumulated predominantly at the peri-infarction site, and were located with the capillary vessels. Capillary vessel density was significantly increased in the SDF-1 group (13.08 +/- 4.11 vessels/mm(2) vs 34.50 +/- 7.59 vessels/mm(2), P = 0.014).

Conclusions: SDF-1 protects against deterioration of cardiac function after acute myocardial infarction by promoting angiogenesis. The safety and long-term prognosis of this treatment remains to be determined.