Abstract 592: Cardioprotection During Ischemia by Induced Coronary Collateral Growth

Abstract

Patients with poorly developed coronary collateral networks have a poorer prognosis after a cardiovascular event than those with well-developed collaterals. The outcome of patients with metabolic syndrome (MetS) was worse than the patient without MetS. Interestingly, coronary collateral growth is impaired in MetS. We hypothesize that coronary collaterals are critical for the cardiac protection in ischemic heart diseases (IHD) and induction of coronary collateral growth (CCG) might ameliorate the outcome of patients with MetS. We study the cardiac protection by coronary collaterals in IHD and the underlying mechanism of impaired CCG in the MetSin a mouse model of CCG. A pneumatic snare was implanted and situated around the LAD. After the mice recovery from the surgery, periodic inflation of the snare occludes the LAD; thus, producing repetitive ischemia (RI). Cardiac function was measure with echocardiography. CCG was measured by myocardial blood flow with contrast echocardiography and by collateral numbers with micro-CT or by vascular density with fluorescence scope. Our preliminary results showed that with occlusion of the LAD, there was no blood flow in the ischemic area. However, after stimulation of CCG by RI, the blood flow the ischemic area was compensated by the grown coronary collaterals and cardiac function was reserved during ischemia. Diabetic mice failed to grow coronary collaterals after RI stimulation and there was no cardiac protection from coronary collaterals during ischemia. Moreover, we studied the roles of growth differentiation factor 11 (GDF11) and miR21 in the regulation of CCG and cardiac protection in IHD. GDF11 was downregulated and miR21 was upregulated in the hearts of Zucker Obese Fatty (ZOF) rats during CCG. We used the Gdf 11 knockout mice and miR 21 knockout mice to study the underlying mechanism. GDF11 is highly expressed in myocardial blood vessels, which suggested the role of GDF11 in vascular growth. Impaired CCG of mice on high fat and high sugar was restored by miR-21 knockout. These data suggest that miR-21 is involved in the impairment of CCG in MetS.