Cardiology; Coronary Disease; Fibrinolysis; Microscopy; Phenotype; Thrombosis; Genetic Therapy; Radiology, Interventional; Nanoparticles
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
Extensive Research Description
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="">48>-/- 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.
NO triggers RGS4 degradation to coordinate angiogenesis and cardiomyocyte growth
Jaba IM, Zhuang ZW, Li N, Jiang Y, Martin KA, Sinusas AJ, Papademetris X, Simons M, Sessa WC, Young LH, Tirziu D. NO triggers RGS4 degradation to coordinate angiogenesis and cardiomyocyte growth. J Clin Invest. 2013 Apr 1;123(4):1718-31
Endothelial Cell-Dependent Regulation of Arteriogenesis
Moraes F, Paye J, Mac Gabhann F, Zhuang ZW, Zhang J, Lanahan A, Simons M. Endothelial Cell-Dependent Regulation of Arteriogenesis. Circ Res. 2013 Jul 29.
Vascular adaptation to a dysfunctional endothelium as a consequence of Shb deficiency
Christoffersson G, Zang G, Zhuang ZW, Vågesjö E, Simons M, Phillipson M, Welsh M. Vascular adaptation to a dysfunctional endothelium as a consequence of Shb deficiency. Angiogenesis. 2012 May 5. [Epub ahead of print]
Macrophage skewing by Phd2 haplodeficiency prevents ischaemia by inducing arteriogenesis
Takeda Y, Costa S, Delamarre E, Roncal C, Leite de Oliveira R, Squadrito ML, Finisguerra V, Deschoemaeker S, Bruyère F, Wenes M, Hamm A, Serneels J, Magat J, Bhattacharyya T, Anisimov A, Jordan BF, Alitalo K, Maxwell P, Gallez B, Zhuang ZW, Saito Y, Simons M, De Palma M, Mazzone M. Macrophage skewing by Phd2 haplodeficiency prevents ischaemia by inducing arteriogenesis. Nature. 2011 Oct 9;479(7371):122-6.
Development and application of a multimodal contrast agent for SPECT/CT hybrid imaging
Criscione JM, Dobrucki LW, Zhuang ZW, Papademetris X, Simons M, Sinusas AJ, Fahmy TM. Development and application of a multimodal contrast agent for SPECT/CT hybrid imaging. Bioconjug Chem. 2011 Sep 21;22(9):1784-92.
FGF-dependent regulation of VEGF receptor 2 expression in mice
Murakami M, Nguyen LT, Hatanaka K, Schachterle W, Chen PY, Zhuang ZW, Black BL, Simons M. FGF-dependent regulation of VEGF receptor 2 expression in mice. J Clin Invest. 2011 Jul;121(7):2668-78. doi: 10.1172/JCI44762.
Challenging the surgical rodent hindlimb ischemia model with the miniinterventional technique
Zhuang ZW, Shi J, Rhodes JM, Tsapakos MJ, Simons M. Challenging the surgical rodent hindlimb ischemia model with the miniinterventional technique. J Vasc Interv Radiol. 2011 Oct;22(10):1437-46.
Tissue-Engineered Lungs for in Vivo Implantation
Petersen TH, Calle EA, Zhao L, Lee EJ, Gui L, Raredon MB, Gavrilov K, Yi T, Zhuang ZW, Breuer C, Herzog E, Niklason LE. Tissue-Engineered Lungs for in Vivo Implantation. Science. 2010 Jul 30;329(5991):538-41. [Epub ahead of print ] PMID: 20576850
VEGF receptor 2 endocytic trafficking regulates arterial morphogenesis
Lanahan AA, Hermans K, Claes F, Kerley-Hamilton JS, Zhuang ZW, Giordano FJ, Carmeliet P, Simons M. VEGF receptor 2 endocytic trafficking regulates arterial morphogenesis. Dev Cell. 2010 May 18;18(5):713-24. PMID: 20434959
ERK1/2-Akt1 crosstalk regulates arteriogenesis in mice and zebrafish
Ren B, Deng Y, Mukhopadhyay A, Lanahan AA, Zhuang ZW, Moodie KL, Mulligan-Kehoe MJ, Byzova TV, Peterson RT, Simons M. ERK1/2-Akt1 crosstalk regulates arteriogenesis in mice and zebrafish. J Clin Invest. 2010 Apr;120(4):1217-28. PMID: 20237411
The FGF system has a key role in regulating vascular integrity
Murakami M, Nguyen LT, Zhuang ZW, Moodie KL, Carmeliet P, Stan RV, Simons M. The FGF system has a key role in regulating vascular integrity. J Clin Invest. 2008 Oct 1;118(10):3355-3366
Arteriogenesis: noninvasive quantification with multi-detector row CT angiography and three-dimensional volume rendering in rodents
Zhuang ZW, Gao L, Murakami M, Pearlman JD, Sackett TJ, Simons M, de Muinck ED. Arteriogenesis: noninvasive quantification with multi-detector row CT angiography and three-dimensional volume rendering in rodents. Radiology. 2006; 240(3):698-707.
Full List of PubMed Publications
- Lee MY, Gamez-Mendez A, Zhang J, Zhuang Z, Vinyard DJ, Kraehling J, Velazquez H, Brudvig GW, Kyriakides TR, Simons M, Sessa WC: Endothelial Cell Autonomous Role of Akt1: Regulation of Vascular Tone and Ischemia-Induced Arteriogenesis. Arterioscler Thromb Vasc Biol. 2018 Feb 15; 2018 Feb 15. PMID: 29449333
- Wang Y, Wu B, Lu P, Zhang D, Wu B, Varshney S, Del Monte-Nieto G, Zhuang Z, Charafeddine R, Kramer AH, Sibinga NE, Frangogiannis NG, Kitsis RN, Adams RH, Alitalo K, Sharp DJ, Harvey RP, Stanley P, Zhou B: Uncontrolled angiogenic precursor expansion causes coronary artery anomalies in mice lacking Pofut1. Nat Commun. 2017 Sep 18; 2017 Sep 18. PMID: 28924218
- Conway DE, Coon BG, Budatha M, Arsenovic PT, Orsenigo F, Wessel F, Zhang J, Zhuang Z, Dejana E, Vestweber D, Schwartz MA: VE-Cadherin Phosphorylation Regulates Endothelial Fluid Shear Stress Responses through the Polarity Protein LGN. Curr Biol. 2017 Jul 24; 2017 Jul 14. PMID: 28712573
- Qi D, Xia Z, Zhuang Z: Metabolic Mechanisms and Potential Therapies of Diabetic Cardiac Complications. J Diabetes Res. 2017; 2017 Jan 15. PMID: 28180129
- Jiang Y, Zhuang Z, Sinusas AJ, Papademetris X: Vascular Tree Reconstruction by Minimizing A Physiological Functional Cost. Conf Comput Vis Pattern Recognit Workshops. 2010 Jun 13. PMID: 21755061
- Yu J, deMuinck ED, Zhuang Z, Drinane M, Kauser K, Rubanyi GM, Qian HS, Murata T, Escalante B, Sessa WC: Endothelial nitric oxide synthase is critical for ischemic remodeling, mural cell recruitment, and blood flow reserve. Proc Natl Acad Sci U S A. 2005 Aug 2; 2005 Jul 25. PMID: 16043715