Molecular mechanisms associated with Angiotensin-converting enzyme-inhibitory peptide activity on vascular extracellular matrix remodeling.
OBJECTIVE
This paper aimed to investigate the molecular mechanisms associated with angiotensin-converting enzyme (ACE)-inhibitory peptide activity involved in vascular extracellular matrix (ECM) remodeling. Therefore, changes in collagen fibers, elastic fibers and laminin were assessed in the left common carotid artery (LCCA).


METHODS
We selected 10-week-old male spontaneously hypertensive rats to study the expression levels of matrix metalloproteinases (MMPs), transforming growth factor, angiotensin (Ang) II and nuclear factor (NF)-p65 in the wall of carotid arteries.


RESULTS
Compared to the control group, laminin expression was significantly increased (p < 0.05) in the vascular endothelium of the LAP (a homemade ACE-inhibitory peptide, named by ourselves) group, whereas the percentage of elastic/collagen fibers in the LCCA vascular area was significantly decreased (p < 0.0001) in the LAP group. Immune blots of MMP-2, MMP-9, NF-p65 and AngII were significantly reduced in the LCCA wall in the LAP group.


CONCLUSIONS
Vascular ECM remodeling may be related to the inhibitory action of LAP on ECM deposition.
Departments of Cardiology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
Hong
H
Fang
Wei
W
Chen
Yang
Y
Gao
Yi
Y
Shen
Ming
M
Luo
D000804:Angiotensin II / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects* / Q000378:metabolism; D017536:Carotid Artery, Common / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004547:Elastic Tissue / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D007249:Inflammation / Q000097:blood; D007781:Lactoferrin / Q000494:pharmacology*; D007797:Laminin / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D051996:Transcription Factor RelA / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D007797:Laminin; D010446:Peptide Fragments; C508962:Tgfb1 protein, rat; D051996:Transcription Factor RelA; D053773:Transforming Growth Factor beta1; C000593249:leucyl-arginyl-prolyl-valyl-alanyl-alanine; D000804:Angiotensin II; D003094:Collagen; D007781:Lactoferrin; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat