The Role of Smooth Muscle Rac1 in Neointimal Formation after Vascular Injury

2013 Fiscal Year Final Research Report

• Project/Area Number: 23790883
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Circulatory organs internal medicine
• Research Institution: Nihon University
• Principal Investigator: LI YUXIN 日本大学, 医学部, 助教 (30599048)
• Project Period (FY): 2011 – 2012
• Keywords: 分子血管病態学 / 血管障害 / 新生内膜

Research Abstract

Four weeks after carotid artery ligation, neointimal formation in smRac1+/- mice was substantially reduced compared to control mice. SmRac1+/- SMCs showed decreased chemotaxis, proliferation with decreased phosphorylation of PAK1, ERK, and reduced ROS production compared to that of control SMCs. Furthermore, the expression of cell cycle-associated genes, such as CyclineA, CyclineE, and CDK4 decreased in SMCs from smRac1+/- mice than that in control mice. Moreover, the expression of SM22, a differentiation marker of smooth muscle and highly expressed in differentiated phenotypes of SMCs, was increased in smRac1+/- mice than that in control mice. These results indicate that SMC Rac1 mediates vessel remodeling after intimal injury through inhibition of SMC migration, proliferation and differentiation. Therapeutic modalities, which target Rac1 in SMCs, therefore, may be beneficial in preventing vascular proliferative diseases.

Research Products

• [Journal Article] Miglitol improves postprandial endothelial dysfunction in patients with acute coronary syndrome and new-onset postprandial hyperglycemia (2013)
  • Author(s): Kitano D, Chiku M, Li Y, Okumura Y, Fukamachi D, Takayama T, Hiro T, Saito S, Hirayama A
  • Journal Title: Cardiovasc Diabetol Volume: 12(1) Pages: 92
  • DOI: 10.1186/1475-2840-12-92
  • Peer Reviewed
• [Journal Article] Plaque stabilization by intensive LDL-cholesterol lowering therapy with atorvastatin is delayed in type 2 diabetic patients with coronary artery disease-Serial angioscopic and intravascular ultrasound analysis (2013)
  • Author(s): Takayama T, Hiro T, Ueda Y, Honye J, Komatsu S, Yamaguchi O, Li Y, Yajima J, Takazawa K, Nanto S, Saito S, Hirayama A, Kodama K
  • Journal Title: J Cardiol Volume: 61 Pages: 381-6
  • DOI: 10.1016/j.jjcc.2013.01.010
  • Peer Reviewed
• [Journal Article] FHL2 prevents cardiac hypertrophy in mice with cardiac-specific deletion of ROCK2 (2013)
  • Author(s): Okamoto R, Li Y, Noma K, Hiroi Y, Liu PY, Taniguchi M, Ito M, Liao JK
  • Journal Title: FASEB J Volume: 27 Pages: 1439-49
  • DOI: 10.1096/fj.12-217018
  • Peer Reviewed
• [Journal Article] Influence of Achieved Low-Density Lipoprotein Cholesterol Level With Atorvastatin Therapy on Stabilization of Coronary Plaques (2012)
  • Author(s): Okada K, Ueda Y, Takayama T, Honye J, Komatsu S, Yamaguchi O, Li Y, Yajima J, Takazawa K, Nanto S, Saito S, Hirayama A, Kodama K
  • Journal Title: Circ J Volume: 76 Pages: 1197-202
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/?term=Circ+J.+2012%3B76%3A1197-202
  • Peer Reviewed
• [Journal Article] Plaque-Stabilizing Effect of Atorvastatin Is Stronger for Plaques Evaluated as More Unstable by Angioscopy and Intravenous Ultrasound (2011)
  • Author(s): Hirayama A, Saito S, Ueda Y, Takayama T, Honye J, Komatsu S, Yamaguchi O, Li Y, Yajima J, Nanto S, Takazawa K, Kodama K
  • Journal Title: Circ J Volume: 75(6) Pages: 1448-54
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/?term=Circ+J.+2011+June%3B75(6)%3A1448-54
  • Peer Reviewed
• [Journal Article] Notch1 in Bone Marrow–Derived Cells Mediates Cardiac Repair After Myocardial Infarction (2011)
  • Author(s): Li Y, Hiroi Y, Ngoy S, Okamoto R, Noma K, Wang CY, Wang HW, Zhou Q, Radtke F, Liao R, Liao JK
  • Journal Title: Circulation Volume: 123 Pages: 866-76
  • DOI: 10.1161/CIRCULATIONAHA.110.947531
  • Peer Reviewed
• [Presentation] Identification of Multiple Biomarkers That Predict the Extent of Plaque Burden in Coronary Culprit Lesions. Symposium (2014)
  • Author(s): Li, Y, et al
  • Organizer: The 78th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Tokyo
  • Year and Date: 20140321-23
• [Presentation] Pleiotropic Effects Of Statin In Stabilization Of Unstable Coronary Plaque - Direct Evidence From Low Density Lipoprotein Receptor Knockout Pig (2013)
  • Author(s): Li Y, et al
  • Organizer: Scientific Sessions 2013 of American Heart Association
  • Place of Presentation: Dallas, Texas
  • Year and Date: 20131116-20
• [Presentation] Development of Unstable Atherosclerotic Lesions in a Novel Low Density Lipoprotein Receptor Knockout Pig (2013)
  • Author(s): Sudo M, Li Y, et al
  • Organizer: The 77th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Yokohama
  • Year and Date: 20130315-17
• [Presentation] Short-term Effect of Miglitol and Voglibose for Postprandial Endothelial Function in Acute Myocardial Infarction Patients with New Onset Postprandial Hyperglycemia (2013)
  • Author(s): Kitano D, Chiku M, Li Y
  • Organizer: The 77th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Yokohama
  • Year and Date: 20130315-17
• [Presentation] Development of Hypercholesterolemia-Induced Complex Unstable Atherosclerotic Lesions in a Novel Low Density Lipoprotein Receptor Knockout Pig (2012)
  • Author(s): Sudo M, Li Y, et al
  • Organizer: Scientific Sessions 2012 of American Heart Association
  • Place of Presentation: Los Angeles, CA
  • Year and Date: 20121103-07
• [Presentation] Critical role of Rho kinase on Aortic Stiffness (2012)
  • Author(s): Li Y, et al
  • Organizer: The 76th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Fukuoka
  • Year and Date: 20120316-18
• [Presentation] Rho Kinase as an Important Mediator of Aortic Stiffness (2011)
  • Author(s): Li Y, et al
  • Organizer: Scientific Sessions 2011 of American Heart Association
  • Place of Presentation: Orlando
  • Year and Date: 20111113-15
• [Presentation] Critical role of smooth muscle Rac1 in neointimal formation after vascular injury (2011)
  • Author(s): Li Y, et al
  • Organizer: The 75th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Yokohama
  • Year and Date: 20110803-04