Homocysteine/Hypertension & Vascular Lesion Formation

Summary

Principal Investigator: Peter H Lin
Abstract: DESCRIPTION (provided by applicant): This proposal describes a 5-year training plan for the development of a research career in academic surgery. The principal investigator has completed structured training in a surgical research fellowship, general surgery residency, vascular surgery fellowship and endovascular fellowship training. The immediate career goal of the principal investigator is to develop research skills through a mentored training regimen that will lead to independent work in the vascular restenosis research relating to cardiovascular risk factors. The long-term goals of the principal investigator are to establish an independent research program that can combine the knowledge of vascular biology and endovascular therapy to further improve the clinical treatment strategy in vascular disease. The proposed research will investigate the molecular interrelationship between two cardiovascular risk factors homocysteine and hypertension in the development of vascular lesions. Dr. Changyi Chen will mentor the principal investigator's scientific research. Dr. Chen is a well-established investigator with four concurrent NIH R01 research grants, and has mentored numerous postdoctoral fellows and young faculty members. To further enhance the training of the principal investigator, the proposal will enlist the expertise of Dr. Joel Morrisett, who is a Professor in the Department of Medicine, Biochemistry and Molecular Physiology, as well as Dr. Cathy Yao, who is an Associate Professor in the Department of Surgery and Microbiology, to provide scientific advice in molecular biology research. The research component will be based on the central hypothesis that hypertension promotes the transport of homocysteine into the vessel wall and hypertension exerts a synergistic effect on homocysteine on vascular cell proliferation, growth factor expression, and vascular lesion formation. The proposed research career development plan has several main components, including coursework in molecular biology and vascular biology, training in advanced molecular biology research techniques, coursework in responsible conduct of research, attending scientific meetings, publishing and presenting research, and a research project which will use the new techniques and knowledge obtained by the principal investigator. The research and training will take place at the Baylor College of Medicine, which is located within the Texas Medical Center, the largest medical center in the world. The Department of Surgery provides an ideal environment for training physician scientists by incorporating expertise from diverse resources and strongly encourages young faculty members to pursue independence through interaction with senior faculty mentors.
Funding Period: 2004-04-01 - 2010-03-31
more information: NIH RePORT

Top Publications

  1. ncbi Neutrophil antimicrobial peptide alpha-defensin causes endothelial dysfunction in porcine coronary arteries
    Panagiotis Kougias
    Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
    J Vasc Surg 43:357-63. 2006
  2. ncbi Comparison of AngioJet rheolytic pharmacomechanical thrombectomy versus AngioJet rheolytic thrombectomy in a porcine peripheral arterial model
    Peter H Lin
    Michael E DeBakey Department of Surgery, Division of Vascular Surgery and Endovascular Therapy, Baylor College of Medicine, VAMC 112, 2002 Holcomb Boulevard, Houston, Texas 77030, USA
    World J Surg 31:715-22. 2007
  3. pmc C-reactive protein increases plasminogen activator inhibitor-1 expression in human endothelial cells
    Changyi Chen
    The Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, United States
    Thromb Res 122:125-33. 2008
  4. pmc Recent advances in molecular mechanisms of abdominal aortic aneurysm formation
    Suman Annambhotla
    Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Michael E DeBakey VA Medical Center, Baylor College of Medicine, Houston, TX 77030, USA
    World J Surg 32:976-86. 2008
  5. pmc Serum amyloid A induces endothelial dysfunction in porcine coronary arteries and human coronary artery endothelial cells
    Xinwen Wang
    Michael E DeBakey Department of Surgery, Baylor College of Medicine, One Baylor Plaza, Mail Stop BCM390, Houston, TX 77030, USA
    Am J Physiol Heart Circ Physiol 295:H2399-408. 2008
  6. ncbi Effect of catheter-directed arterial embolization and laparoscopic endovascular stapling on stapled vessel integrity in a porcine model
    Edward P Dominguez
    Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA
    Vascular 16:80-4. 2008
  7. pmc Ceramide: a common pathway for atherosclerosis?
    Jean Bismuth
    Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, United States
    Atherosclerosis 196:497-504. 2008
  8. pmc Chlorotyrosine promotes human aortic smooth muscle cell migration through increasing superoxide anion production and ERK1/2 activation
    Hong Mu
    Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Baylor College of Medicine, and Michael E DeBakey VA Medical Center, Houston, TX 77030, United States
    Atherosclerosis 201:67-75. 2008
  9. pmc Nitrotyrosine promotes human aortic smooth muscle cell migration through oxidative stress and ERK1/2 activation
    Hong Mu
    Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA
    Biochim Biophys Acta 1783:1576-84. 2008
  10. pmc Capsaicin blocks HIV protease inhibitor ritonavir-induced vascular dysfunction in porcine pulmonary arteries
    Ajay K Dhadwal
    Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, U S A
    Med Sci Monit 15:BR1-5. 2009

Detail Information

Publications32

  1. ncbi Neutrophil antimicrobial peptide alpha-defensin causes endothelial dysfunction in porcine coronary arteries
    Panagiotis Kougias
    Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
    J Vasc Surg 43:357-63. 2006
    ....
  2. ncbi Comparison of AngioJet rheolytic pharmacomechanical thrombectomy versus AngioJet rheolytic thrombectomy in a porcine peripheral arterial model
    Peter H Lin
    Michael E DeBakey Department of Surgery, Division of Vascular Surgery and Endovascular Therapy, Baylor College of Medicine, VAMC 112, 2002 Holcomb Boulevard, Houston, Texas 77030, USA
    World J Surg 31:715-22. 2007
    ..This study compares the acute and chronic vessel wall response and hemolysis due to conventional AngioJet rheolytic thrombectomy (RT) and AngioJet PMT in the porcine peripheral arterial model...
  3. pmc C-reactive protein increases plasminogen activator inhibitor-1 expression in human endothelial cells
    Changyi Chen
    The Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, United States
    Thromb Res 122:125-33. 2008
    ..CRP also increased its receptor CD32 expression which may further enhance its action. CRP-induced PAI-1 expression may be mediated by oxidative stress and p38 signal pathway as antioxidant effectively blocks the effect of CRP on HCAEC...
  4. pmc Recent advances in molecular mechanisms of abdominal aortic aneurysm formation
    Suman Annambhotla
    Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Michael E DeBakey VA Medical Center, Baylor College of Medicine, Houston, TX 77030, USA
    World J Surg 32:976-86. 2008
    ..This review will be helpful to those who want to recognize the newest endeavors within the field and identify possible lines of investigation in AAA...
  5. pmc Serum amyloid A induces endothelial dysfunction in porcine coronary arteries and human coronary artery endothelial cells
    Xinwen Wang
    Michael E DeBakey Department of Surgery, Baylor College of Medicine, One Baylor Plaza, Mail Stop BCM390, Houston, TX 77030, USA
    Am J Physiol Heart Circ Physiol 295:H2399-408. 2008
    ..These findings suggest that SAA may contribute to the progress of coronary artery disease...
  6. ncbi Effect of catheter-directed arterial embolization and laparoscopic endovascular stapling on stapled vessel integrity in a porcine model
    Edward P Dominguez
    Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA
    Vascular 16:80-4. 2008
    ..Such a practice appears to be unsafe based on our findings and should be performed with caution in a clinical setting...
  7. pmc Ceramide: a common pathway for atherosclerosis?
    Jean Bismuth
    Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, United States
    Atherosclerosis 196:497-504. 2008
    ..Furthermore, the potential therapeutic implications of modulating ceramide concentrations are also discussed...
  8. pmc Chlorotyrosine promotes human aortic smooth muscle cell migration through increasing superoxide anion production and ERK1/2 activation
    Hong Mu
    Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Baylor College of Medicine, and Michael E DeBakey VA Medical Center, Houston, TX 77030, United States
    Atherosclerosis 201:67-75. 2008
    ..Thus, these findings demonstrate new biological functions of chlorotyrosine in human SMC migration, which may play a crucial role in the vascular lesion formation...
  9. pmc Nitrotyrosine promotes human aortic smooth muscle cell migration through oxidative stress and ERK1/2 activation
    Hong Mu
    Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA
    Biochim Biophys Acta 1783:1576-84. 2008
    ..Nitrotyrosine may contribute to cardiovascular pathogenesis...
  10. pmc Capsaicin blocks HIV protease inhibitor ritonavir-induced vascular dysfunction in porcine pulmonary arteries
    Ajay K Dhadwal
    Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, U S A
    Med Sci Monit 15:BR1-5. 2009
    ..The objective of this study was to determine whether capsaicin, a major ingredient of hot pepper with antioxidative property, could effectively inhibit ritonavir-induced oxidative injury in porcine pulmonary arteries...
  11. pmc Covalent linkage of heparin provides a stable anti-coagulation surface of decellularized porcine arteries
    Dan Liao
    Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Baylor College of Medicine, and Michael E DeBakey VA Medical Center, Houston, TX 77030, USA
    J Cell Mol Med 13:2736-43. 2009
    ..This study may suggest a new strategy to develop tissue-engineered biological vascular grafts, which could be used for human coronary or low extremity artery bypasses...
  12. pmc Growth hormone-releasing peptide ghrelin inhibits homocysteine-induced endothelial dysfunction in porcine coronary arteries and human endothelial cells
    Nasim Hedayati
    Michael E DeBakey Department of Surgery, Division of Vascular Surgery and Endovascular Therapy, Molecular Surgeon Research Center, Baylor College of Medicine, Houston, Texas 77030 3411, USA
    J Vasc Surg 49:199-207. 2009
    ..This study investigated the effect and potential mechanisms of ghrelin on Hcy-induced endothelial dysfunction...
  13. pmc Lactosylceramide causes endothelial dysfunction in porcine coronary arteries and human coronary artery endothelial cells
    Jean Bismuth
    Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
    Med Sci Monit 15:BR270-4. 2009
    ..The goal of this study was to determine the effects and molecular mechanisms of LacCer on endothelial functions in porcine coronary arteries and human coronary endothelial cells (HCAECs)...
  14. pmc Role of somatic mutations in vascular disease formation
    Sarah M Weakley
    Michael E DeBakey Department of Surgery, Molecular Surgeon Research Center, Baylor College of Medicine, One Baylor Plaza, Mail Stop BCM391, Houston, TX 77030, USA
    Expert Rev Mol Diagn 10:173-85. 2010
    ....
  15. pmc The soybean isoflavonoid equol blocks ritonavir-induced endothelial dysfunction in porcine pulmonary arteries and human pulmonary artery endothelial cells
    Charlie Cheng
    Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
    J Nutr 140:12-7. 2010
    ..These novel data suggest that equol may have a clinical application in preventing HIV-associated cardiovascular complications...
  16. ncbi Current update on HIV-associated vascular disease and endothelial dysfunction
    Hong Mu
    Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Baylor College of Medicine, One Baylor Plaza, Mail stop NAB 2010, Houston, Texas 77030, USA
    World J Surg 31:632-43. 2007
    ....
  17. ncbi Cyclic strain induces vascular smooth muscle cell differentiation from murine embryonic mesenchymal progenitor cells
    Gordon M Riha
    Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
    Surgery 141:394-402. 2007
    ..However, the underlying molecular mechanisms are largely unknown. The objective of this study was to test our hypothesis that cyclic strain could affect smooth muscle cell (SMC) differentiation...
  18. ncbi Ginkgolide A attenuates homocysteine-induced endothelial dysfunction in porcine coronary arteries
    Wei Zhou
    Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
    J Vasc Surg 44:853-62. 2006
    ..The objective of this study was to investigate whether ginkgolide A (GA), a major constituent of Ginkgo biloba, could block homocysteine-induced endothelial dysfunction in porcine coronary arteries...
  19. ncbi Effects of homocysteine and ginsenoside Rb1 on endothelial proliferation and superoxide anion production
    Ryuji Ohashi
    Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Molecular Surgeon Research Center, Baylor College of Medicine, Houston, Texas 77030, USA
    J Surg Res 133:89-94. 2006
    ..In the present study, we investigated the effect of Hcy on endothelial proliferation and a protective effect of ginsenoside Rb1 on the action of Hcy...
  20. ncbi Lymphotoxin-alpha and cardiovascular disease: clinical association and pathogenic mechanisms
    Joseph J Naoum
    Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA
    Med Sci Monit 12:RA121-4. 2006
    ..More clinical and basic science studies are warranted to further understand the role of LTalpha in cardiovascular disease...
  21. ncbi Mouse models of neointimal hyperplasia: techniques and applications
    Xinwen Wang
    Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
    Med Sci Monit 12:RA177-85. 2006
    ..Thus, this review provides updated information and helps vascular surgeons and other vascular biologists in selecting appropriate mouse models for their research on neointimal hyperplasia...
  22. ncbi Adipokine resistin promotes in vitro angiogenesis of human endothelial cells
    Hong Mu
    Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Baylor College of Medicine, One Baylor Plaza, Mail stop NAB 2010, Houston, Texas 77030, USA
    Cardiovasc Res 70:146-57. 2006
    ..In the present study, we evaluated the effects of resistin on angiogenic potential, including endothelial cell proliferation, migration, and capillary-like tube formation...
  23. ncbi CD40 ligand increases expression of its receptor CD40 in human coronary artery endothelial cells
    Hong Chai
    Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
    Surgery 140:236-42. 2006
    ..The aim of this study was to investigate whether CD40L could affect the expression of its membrane receptor CD40 as a feedback mechanism by which CD40L could enhance its functions in human coronary artery endothelial cells (HCAECs)...
  24. ncbi Lysophosphatidylcholine and secretory phospholipase A2 in vascular disease: mediators of endothelial dysfunction and atherosclerosis
    Panagiotis Kougias
    Michael E DeBakey Department of Surgery, Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Baylor College of Medicine, Houston, TX 77030, U S A
    Med Sci Monit 12:RA5-16. 2006
    ..LPC and sPLA(2)-II are two very important mediators in atherosclerosis. Further research is warranted to clarify the cellular and molecular mechanisms that underlie their actions and to correlate in vitro data with clinical observations...
  25. ncbi Thymosin beta10 inhibits cell migration and capillary-like tube formation of human coronary artery endothelial cells
    Hong Mu
    Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA
    Cell Motil Cytoskeleton 63:222-30. 2006
    ..This study suggests a potential therapeutic application of thymosin beta10 to the diseases with excessive angiogenesis such as cancer...
  26. ncbi Chronically impaired endothelial vasoreactivity following oversized endovascular introducer sheath placement in porcine iliac arteries: implications for endovascular therapy
    Peter H Lin
    Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
    Vascular 14:353-61. 2006
    ..Our study underscores the importance of appropriate patient selection to minimize potential sheath oversize and endograft device miniaturization to avoid vessel wall injury and maintain vasoreactivity...
  27. ncbi Nitrotyrosine and chlorotyrosine: clinical significance and biological functions in the vascular system
    Imran Mohiuddin
    Michael E DeBakey Department of Surgery, Division of Vascular Surgery and Endovascular Therapy, Molecular Surgeon Research Center, Baylor College of Medicine, Houston, Texas 77030, USA
    J Surg Res 133:143-9. 2006
    ..This review will focus on the formation, clinical significance, and animal and cell-culture models of these important molecules...
  28. ncbi Rheolytic pharmacomechanical thrombectomy in experimental chronic deep vein thrombosis: effect of L-arginine on thrombogenicity and endothelial vasomotor function
    Peter H Lin
    Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston VAMC 112, 2002 Holcomb Blvd, Houston, Texas 77030, USA
    World J Surg 31:664-75. 2007
    ....
  29. ncbi Development of small-diameter vascular grafts
    Xinwen Wang
    Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Baylor College of Medicine, NAB 2010, Houston, Texas 77030, USA
    World J Surg 31:682-9. 2007
    ..For instance, a completely cellular approach culturing cells into tissue sheets and wrapping these layers was able to form a layered cellular vascular graft with impressive strength...
  30. ncbi Growth related oncogene-alpha (GRO-alpha): roles in atherosclerosis, angiogenesis and other inflammatory conditions
    Carlos Bechara
    Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
    Med Sci Monit 13:RA87-90. 2007
    ..We hope to further evaluate this molecule in the pathogenesis of atherosclerosis as well as angiogenesis to promote a background for therapeutic interventions...
  31. ncbi Growth-related oncogene-alpha induces endothelial dysfunction through oxidative stress and downregulation of eNOS in porcine coronary arteries
    Carlos Bechara
    Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
    Am J Physiol Heart Circ Physiol 293:H3088-95. 2007
    ..Thus GRO-alpha impairs endothelium-dependent vasorelaxation in porcine coronary arteries through a mechanism of overproduction of superoxide anion and downregulation of eNOS. GRO-alpha may contribute to human coronary artery disease...
  32. pmc Arterial baroreceptors in the management of systemic hypertension
    Panagiotis Kougias
    Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA
    Med Sci Monit 16:RA1-8. 2010
    ..lt;br />..