Title(s): Assistant Professor of Medicine (Cardiology) and of Physiology
Department(s): Medicine Physiology
Education: University of Groningen, Groningen, The Netherlands M.D. 1983 Medicine University of Groningen, Groningen, The Netherlands Ph.D. 1994 Cardiology
Programs: Angiogenesis Research Center Program in Experimental and Molecular Medicine
Maurice RL, Fromageau J, Cardinal MH, Doyley M, de Muinck E, Robb J, Cloutier G. Characterization of Atherosclerotic Plaques and Mural Thrombi with Intravascular Ultrasound Elastography: A Potential Method Evaluated in an Aortic Rabbit Model and a Human Coronary Artery. IEEE-TITB 2008;12:290-298.
de Muinck ED, Nagy N, Tirziu D, Murakami M, Gurusamy N, Goswamy SK, Ghatpande S, Engelman RN, Das DK, Simons M. Protection Against Myocardial Ischemia–Reperfusion Injury by the Angiogenic Masterswitch Protein PR 39 Gene Therapy: The Roles of HIF1α Stabilization and FGFR1 Signaling. Antioxidants & Redox Signaling 2007;9:437-445.
Sherman JA, Hall A, Malenka DJ, De Muinck ED, Simons M. Humoral and cellular factors responsible for coronary collateral formation. Am J Cardiol. 2006 Nov 1;98(9):1194-7. Epub 2006 Aug 31. (view details on MedLine)
Buehler A, van Zandvoort MA, Stelt BJ, Hackeng TM, Schrans-Stassen BH, Bennaghmouch A, Hofstra L, Cleutjens JP, Duijvestijn A, Smeets MB, de Kleijn DP, Post MJ, de Muinck ED. cNGR: a novel homing sequence for CD13/APN targeted molecular imaging of murine cardiac angiogenesis in vivo. Arterioscler Thromb Vasc Biol. 2006 Dec;26(12):2681-7. Epub 2006 Sep 21. (view details on MedLine)
Mandinov L, Moodie KL, Mandinova A, Zhuang Z, Redican F, Baklanov D, Lindner V, Maciag T, Simons M, de Muinck ED. Inhibition of in-stent restenosis by oral copper chelation in porcine coronary arteries. Am J Physiol Heart Circ Physiol. 2006 Dec;291(6):H2692-7. Epub 2006 May 26. (view details on MedLine)
Baklanov DV, Moodie KM, McCarthy FE, Mandrusov E, Chiu J, Aswonge G, Cheng J, Chow M, Simons M, de Muinck ED. Comparison of transendocardial and retrograde coronary venous intramyocardial catheter delivery systems in healthy and infarcted pigs. Catheter Cardiovasc Interv. 2006 Sep;68(3):416-23. (view details on MedLine)
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 Sep;240(3):698-707. (view details on MedLine)
de Muinck ED, Thompson C, Simons M. Progress and prospects: cell based regenerative therapy for cardiovascular disease. Gene Ther. 2006 Apr;13(8):659-71. Review. (view details on MedLine)
de Muinck ED, Simons M. Calling on reserves: granulocyte colony stimulating growth factor in cardiac repair. Circulation. 2005 Nov 15;112(20):3033-5. (view details on MedLine)
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;102(31):10999-1004. Epub 2005 Jul 25. (view details on MedLine)
Professional Interests:
My laboratory is a translational lab. with a focus on understanding and measuring the impact of CD13/APN as announced by molecular imaging on neo-vascularization, ischemic wound healing, perfusion, oxygenation and function of the heart.
We have demonstrated that angiogenic vasculature in the heart can be targeted and imaged using a synthetic peptide sequence consisting of asparagine-glycine-arginine (NGR). The vascular address for this homing sequence is a cell surface metalloprotease, aminopeptidase N (APN) also known as CD13/APN, and we found that newly formed blood vessel can be targeted and imaged using conjugates of NGR with different fluorescent molecules. As a translational step towards clinical application of this imaging modality, we are establishing this method in the porcine chronic myocardial ischemia model using NGR decorated iron-oxide nanoparticles that are detectable by MR imaging. We are identifying the stage of vascular development that is announced by CD13/APN expression and in order to measure the impact of these neo-vessels on perfusion, oxygenation and function we use a multi-modal imaging approach that includes functional and perfusion sensitive MR imaging, tissue pO2 and oxygen free radical measurements by electron paramagnetic resonance (EPR) imaging, micro-PET with oxygen sensitive tracers and flow measurements with ultrasound contrast. The impact of vessel density and anatomy of the vascular tree on these parameters is measured by micro-CT.
The possibility of treating and monitoring therapeutic effect at the same target is appealing and therefore our goal is to favorably alter wound healing after ischemic injury with NGR decorated particles carrying a ‘payload’ of a therapeutic that modifies the wound healing process focusing on collagen deposition as a first step.
In addition we have shown that CD13/APN is present on blood vessels in human atherosclerotic plaque and we are currently developing an intra-vascular ultrasound (IVUS) based multi-modal imaging method that combines standard IVUS imaging with elastography and targeted imaging of plaque vasculature with ultrasound contrast.
Finally, in our search to understand the role of CD13/APN in neo-vascularization we have recently discovered in collaboration with Dr. Jose Conejo-Garcia from the Department of Microbiology and Immunology, that CD11c dendritic cells are present in the healing murine myocardial infarct. These cells are practically all CD13/APN positive (95%) and express the canonical endothelial marker VE-Cadherin. Thus, for the first time we show the contribution of pure hematopoietic cells to cardiac angiogenesis and their ability to acquire an endothelial phenotype indicating a thus far unrecognized plasticity of these cells. The high proportion of DC indicates a previously unnoticed role of immune cells in cardiac neo-vascularization. The observation that cells of myeloid origin (DC) participate in neo-vascularization could be an indication that embryonic mechanisms of vasculogenesis are recapitulated in adult organisms.
Courses Taught:
Medical School
Cardiovascular physiology in Medical Physiology 110
Pharmacology small group (2 nd year med. students)
Advanced Medical Sciences ( 4 th year med. students)
Graduate Program in Experimental and Molecular Medicine: Advanced Systems Physiology (PEMM 271)
Thayer School of Engineering
Cardiovascular Imaging (undergraduate level, ENGS 10)