UTHSC Vascular Biology Center




	Chunxiang Zhang, M.D., Ph.D., Assistant Professor and Director, Vascular Injury Core Laboratory
	Vascular Injury Laboratory Vascular injury plays a key role in the pathogenesis of atherosclerosis, coronary heart disease, restenosis, hypertension, stroke, ischemia-reperfusion injury and diabetic vascular complications. The VBCE vascular injury laboratory, directed by Dr. Chunxiang Zhang, functions as a laboratory for vascular injury related bench and pre-clinical research. Activities in the laboratory include: construction of diverse vascular injury animal models, catheter-based drug and gene delivery, histology and morphometric analysis and immunohistochemistry. The primary goals are to discover and understand the mechanisms underlying vascular injury and to develop new therapies for the treatment and prevention of injury-related vascular disease. By integrating research and discovery efforts in basic molecular and cell biology with pre-clinical investigations, new discoveries will lead to promising therapies for the treatment of vascular diseases. Angioplasty Related Vascular Injury Models Since the birth of coronary angioplasty 20 years ago, percutaneous transluminal coronary angioplasty (PTCA) and peripheral artery angioplasty (PTA) have become widely adapted treatments for coronary and peripheral artery diseases. More than one 1.5 million patients will receive PTCA or PTA every year in the world. PTCA and PTA, however, are often complicated by restenosis (luminal renarrowing) (Fig. 1), which occurs in 30-50 % of patients despite a successful procedure. Approximately 250,000 patients develop restenosis in the United States every year, thus affecting the success of the procedure as well as producing a significant impact on health-care costs. A limited number of drugs and devices have been used to overcome restenosis but to date have not particularly successful. Animal vascular injury models are crucial in studying the mechanism of restenosis and testing the therapeutic effects of pharmacological agents and endovascular devices. In the past year, four angioplasty-related vascular injury models were set up in the Vascular Injury Laboratory: rabbit iliac and carotid artery balloon injury, rat carotid artery balloon injury, mouse carotid artery ligation and guidewire injury. Restenosis After Angioplasty Ischemia Injury Induced Angiogenesis Models Considerable advances in both surgical bypass and percutaneous revascularization techniques have been achieved in the treatment of coronary artery disease and peripheral arterial disease. Many patients with ischemic vascular disease are not suitable for conventional revascularization, and therefore alternative therapeutic strategies are necessary. Collateral Vessel in the Heart Therapeutic angiogenesis, which consists of stimulating collateral vessel growth (Fig. 3) in to ischemic heart and limb, is an innovative approach in the treatment of coronary disease. Currently, therapeutic angiogenesis achieves revascularization by administration of angiogenic growth factor proteins or genes. Among the growth factors that play a role in blood vessel growth and development, vascular endothelial growth factors (VEGFs) and fibroblast growth factor have been the most widely studied. Preliminary animal experiments of VEGF are promising with evidence of capillary formation at the target myocardium have been promising with evidence of capillary formation at the target myocardium and limb after growth factor administration. Real efficacy, however, has not been proven and the potential side-effects of these potent angiogenic growth factors remain a concern. Initial phase I and II clinical trials are currently underway to evaluate these factors. Most importantly, the molecular mechanisms of angiogenesis are still not clear and new angiogenic growth factors together with their signal trasduction pathways need to be identified. Rabbit and rat myocardial infarction models via coronary artery ligation and the ischemic limb model of rabbit, rat or mouse via the femoral artery excision are two ischemia injury-induced angiogenesis models carried out in the laboratory. Vessel density in ischemic areas are detected by immunohistochemistry with antibodies for endothelial cell markers (fig 4), angiography (fig 5) and laser Doppler flowmetry. Animal Models of Atherosclerosis Atherosclerosis is a chronic complicated lesion in which vascular injuries, including inflammatory injury, play important roles (Fig. 7). The American Heart Association reports that atherosclerosis is the leading cause of death in the United States and the cause of more than half of all mortality in the world’s developed countries. Recent studies, using high cholesterol diet-induced rabbit atherosclerosis and genetic forms of atherosclerotic mouse models, in the injury lab have found that local incubation with high concentration of lysophosphatidic acid (LPA) can induce atherosclerosis-like neointima formation both in rats and mice (Fig. 8). These models show promise as new in the fight against atherosclerosis. Vascular dysfunction is a precursor to the development of atherosclerosis (fig 9), hypertension, ischemia-reperfusion injury, diabetic vascular complications and vascular aging. Dysfunction may also serve as a marker for vascular injury under these pathological conditions. In vivo studies are currently underway to study vascular function and dysfunction by using an isolated organ perfusion system and Doppler flowmetry to elucidate the mechanisms underlying the pathogenesis of these diseases (fig 10). Catheter-based Drug and Gene Delivery System Vascular target drug and gene delivery is very important to obtain maximal therapeutic effects and reduce any potential systemic side effects. The core laboratory has set up a catheter-based drug and gene delivery system by temporary ligation of target vessel segment or using the perfusion catheter. Osmotic minipump connected with catherter was used for the long-time delivery of some specific compounds. Ongoing Collaborative Research Projects CD9 and Vascular Injury Responses PTP-1B and Vascular Injury Responses Angiotension II-Related Signaling and Vascular Injury Responses LPA in Atherosclerosis MPO in Vascular dysfunction, Atherosclerosis and Restenosis Sprouty in Vascular Injury Responses The Development of a New Anti-restenosis Endovascular Device Gene Therapy for Restenosis After Balloon Injury and Diabetic Angiogenesisn [HOME] [CENTER] [DIRECTOR] [FACULTY] [WORKING GROUP] [INJURY LAB] [TAM] [TAM INVESTIGATORS] [TAM TRIALS] [NEWS] [GIVING]