Zhenwu Zhuang, MD, MS

Dr. Zhuang’s research interests include multi-modality imaging in the cardiovascular system, the neurovascular system, and tumors. Currently his research is focusing on developing of micro-imaging approaches (microCT and micro-SPECT) for the assessment of angiogenesis, arteriogenesis, and vascular remolding. Because of his interventional radiologist’s background, he is also interested in the translational research to develop strategies for local gene or cellular therapies and evaluate the therapeutic efficacy using noninvasive imaging approaches.

Specialized Terms: Angiogenesis; Arteriogenesis; Vascular/Cardiac Remolding; Vascular Integrity; MicroCT; Micro-SPECT; MR; Molecular Imaging; Interventional Cardiology/Radiology; Gene Therapy; Cell Therapy; Cardiac Repair; Phenotype; Cardiovascular Development; Lung; Tumor; Nanoparticle; Thrombosis; Fibrinolysis; Coronary microvascular disease; Factor XIII

Exercise-induced Vascular Changes are eNOS-NO Dependent in Mice with Hindlimb Ischemia. Exercise training is assumed to improve skeletal muscle function in the presence of peripheral arterial disease (PAD); however, the mechanisms are unclear. Nitric oxide (NO) plays an important role in the cardiovascular system in response to ischemic injury; however, controversy remains regarding the role of endothelial NO synthase (eNOS)-derived NO on angiogenesis, arteriogenesis, and vascular integrity after exercise. We have discovered that ^99mTc-labeled RGD-peptide (activated av integrins) uptake was increased with hindlimb ischemia compared to sedentary mice both in wild type and eNOS^-/- mice, however, swimming increased uptake of radiolabeled peptide only in eNOS^-/- mice after hindlimb ischemia following swimming training. This later increase was associated with decreased capillary density and increased arteriogenesis (<48 _c2b5_m29_.="" in="" vivo="" contrast="" micro-computed="" tomography="" demonstrated="" late="" retention="">^-/- hindlimb ischemia mice suggesting disruption of vascular integrity, which worsened with swimming training. So we believe that Integrin activation was greater in eNOS^-/- hindlimb ischemia mice and was augmented with swimming. However, this increase was associated with disruption of vascular integrity. NO does appear to play a role in the effects of exercise training in a model of PAD.

Novel molecular imaging for early detection of microthrombi in microvasculature. The exact mechanism and importance of coronary microvascular disease (MVD), under conditions of ischemic injury, are still unclear. Based on two notions: 1) endothelial cell can be damaged and platelets can be activated by photosensitizers irradiated by specific wavelength of laser in the heart of a mouse; 2) coagulation factor XIII is required for the impairment of microvascular function progress, we are establishing a novel animal model of MVD and applying non-invasive imaging strategy to dynamically monitor cross-linking thrombi formation and to document subsequent cardiac function in rodents following ischemic injury.