title: Regulation of MMP/TIMP by HUVEC transplantation attenuates ventricular remodeling in response to myocardial infarction.
abstract: OBJECTIVE
  We elucidated the therapeutic potential of human umbilical vein endothelial cells (HUVECs) for ameliorating progressive heart failure in a myocardial infarction (MI) rat model.
  
  
  METHODS
  MI was induced by ligation of left anterior descending artery, and HUVEC was transplanted 1week after MI. Cardiac function was evaluated by echocardiography, and histological analyses were performed.
  
  
  RESULTS
  Phosphate-buffered saline (MI-V, n=5) or HUVEC (MI-HV, n=5) were injected into the border zone and infarcted area 7days after ligation of the left coronary artery in rats. The MI-HV group showed attenuation of left ventricular (LV) remodeling compared with the MI-V group. In the infarcted myocardium, a few of injected HUVEC was retained up to 28days. The ratios of matrix metalloproteinase (MMP)-2 or MMP-9 to tissue inhibitor of metalloproteinase (TIMP)-1 or TIMP-3 were decreased in the MI-HV group compared with the MI-V group. In vivo zymography analysis showed that HUVEC transplantation decreased the activities of MMP-2 and MMP-9. In immunohistochemistry, decreased MMP-2 and increased TIMP-1 and TIMP-3 expression were observed at 48h after HUVEC transplantation. These effects on MMP/TIMP balance were inhibited by L-NAME administration (an eNOS inhibitor, 10mg/kg). NOS inhibition decreased the protein expressions of TIMP-1 and TIMP-3 but did not change the protein expressions of MMP-2 and MMP-9.
  
  
  CONCLUSIONS
  Our data suggest that altered balance between MMP and TIMP by HUVEC transplantation contributed to attenuation of ventricular remodeling after MI via eNOS.
authors.affiliation: Research Laboratory of Cardiovascular Regeneration, Chonnam National University Hospital, Gwangju, Republic of Korea.
authors.forename: Jin-Sook
authors.initials: JS
authors.lastname: Kwon
authors.affiliation: Research Laboratory of Cardiovascular Regeneration, Chonnam National University Hospital, Gwangju, Republic of Korea.
authors.forename: Yong Sook
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Research Laboratory of Cardiovascular Regeneration, Chonnam National University Hospital, Gwangju, Republic of Korea.
authors.forename: Ae Shin
authors.initials: AS
authors.lastname: Cho
authors.affiliation: Research Laboratory of Cardiovascular Regeneration, Chonnam National University Hospital, Gwangju, Republic of Korea.
authors.forename: Hyang Hee
authors.initials: HH
authors.lastname: Cho
authors.affiliation: Research Laboratory of Cardiovascular Regeneration, Chonnam National University Hospital, Gwangju, Republic of Korea.
authors.forename: Jeong Sook
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Research Laboratory of Cardiovascular Regeneration, Chonnam National University Hospital, Gwangju, Republic of Korea.
authors.forename: Moon Hwa
authors.initials: MH
authors.lastname: Hong
authors.affiliation: Research Laboratory of Cardiovascular Regeneration, Chonnam National University Hospital, Gwangju, Republic of Korea; Center of Molecular Medicine, Graduate School, Chonnam National University, Republic of Korea.
authors.forename: Hye-Yun
authors.initials: HY
authors.lastname: Jeong
authors.affiliation: Research Laboratory of Cardiovascular Regeneration, Chonnam National University Hospital, Gwangju, Republic of Korea; Center of Molecular Medicine, Graduate School, Chonnam National University, Republic of Korea.
authors.forename: Wan Seok
authors.initials: WS
authors.lastname: Kang
authors.affiliation: Department of Cardiology, College of Medicine, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Kyung-Kuk
authors.initials: KK
authors.lastname: Hwang
authors.affiliation: Department of Cardiology, College of Medicine, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Jang-Whan
authors.initials: JW
authors.lastname: Bae
authors.affiliation: Department of Cardiology, Chonnam National University Hospital, Gwangju, Republic of Korea.
authors.forename: Myung Ho
authors.initials: MH
authors.lastname: Jeong
authors.affiliation: Department of Cardiology, College of Medicine, Chungbuk National University, Cheongju, Republic of Korea. Electronic address: mccho@chungbuk.ac.kr.
authors.forename: Myeong-Chan
authors.initials: MC
authors.lastname: Cho
authors.affiliation: Research Laboratory of Cardiovascular Regeneration, Chonnam National University Hospital, Gwangju, Republic of Korea; Department of Cardiology, Chonnam National University Hospital, Gwangju, Republic of Korea. Electronic address: cecilyk@hanmail.net.
authors.forename: Youngkeun
authors.initials: Y
authors.lastname: Ahn
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000637:transplantation*; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D009203:Myocardial Infarction / Q000378:metabolism* / Q000628:therapy; D009206:Myocardium / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000378:metabolism*; D020257:Ventricular Remodeling
chemical_list: D004791:Enzyme Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D019717:Tissue Inhibitor of Metalloproteinase-3; D019001:Nitric Oxide Synthase; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; D019331:NG-Nitroarginine Methyl Ester
keywords: Human umbilical vein endothelial cell; Matrix metalloproteinase; Myocardial infarction; Remodeling