Shear-stress and wall-stress regulation of vascular remodeling after balloon angioplasty: effect of matrix metalloproteinase inhibition.
BACKGROUND
Constrictive vascular remodeling (VR) is the most significant component of restenosis after balloon angioplasty (PTA). Whereas in physiological conditions VR is associated with normalization of shear stress (SS) and wall stress (WS), after PTA the role of SS and WS in VR is unknown. Furthermore, whereas matrix metalloproteinase inhibition (MMPI) has been shown to modulate VR after PTA, its effect on the SS and WS control mechanisms after PTA is unknown.


RESULTS
PTA was performed in external iliac arteries of 12 atherosclerotic Yucatan pigs, of which 6 pigs (7 vessels) received the MMPI batimastat and 6 pigs (10 vessels) served as controls. Before and after the intervention and at 6-week follow-up, intravascular ultrasound pullback was performed, allowing 3D reconstruction of the treated segment and computational fluid dynamics to calculate the media-bounded area and SS. WS was derived from the Laplace formula. Immediately after PTA, media-bounded area, WS, and SS changed by 20%, 16%, and -49%, respectively, in both groups. VR was predicted by SS and WS. In the control group, SS and WS had been normalized at follow-up with respect to the reference segment. In contrast, for the batimastat group, the SS had been normalized, but not the WS. The latter is attributed to an increase in wall area at follow-up.


CONCLUSIONS
Vascular remodeling after PTA is controlled by both SS and WS. MMPI inhibited the WS control system.
Wentzel
J J
JJ
Department of Cardiology, Thoraxcenter Rotterdam, The Netherlands.
Kloet
J
J
Andhyiswara
I
I
Oomen
J A
JA
Schuurbiers
J C
JC
de Smet
B J
BJ
Post
M J
MJ
de Kleijn
D
D
Pasterkamp
G
G
Borst
C
C
Slager
C J
CJ
Krams
R
R
D000800:Angioplasty, Balloon; D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D005246:Feedback; D018056:Hemorheology; D007083:Iliac Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000601:surgery; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008955:Models, Cardiovascular; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology; D012044:Regression Analysis; D013314:Stress, Mechanical; D013556:Swine, Miniature; D013876:Thiophenes / Q000494:pharmacology*; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology; D014463:Ultrasonography; D014654:Vascular Patency / Q000187:drug effects
D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D013876:Thiophenes; D010649:Phenylalanine; C080985:batimastat; D020782:Matrix Metalloproteinases