Mice lacking the gene encoding for MMP-9 and resistance artery reactivity.
OBJECTIVE
To define the link between the deletion of gene encoding for metalloproteinase 9 and resistance artery reactivity, we studied in vitro smooth muscle and endothelial cell function in response to pressure, shear stress, and pharmacological agents.


BACKGROUND
Matrix metalloproteinases play a crucial role in the regulation of extracellular matrix turnover and structural artery wall remodeling.


METHODS
Resistance arteries were isolated from mice lacking gene encoding for MMP-9 (KO) and their control (WT). Hemodynamic, pharmacology approaches, and Western blot analysis were used in this study.


RESULTS
The measurement of blood pressure in vivo was similar in KO and WT mice. Pressure-induced myogenic tone, contractions to angiotensin-II and phenylephrine were similar in both groups. The inhibition of MMP2/9 ((2R)-2-[(4-biphenylylsulfonyl) amino]-3-phenylpropionic acid) significantly decreased myogenic tone in WT and had no effect in KO mice. Relaxation endothelium-dependent (flow-induced- dilation 41.3+/-0.6 vs. 21+/-1.6 at 10 microl/min in KO and WT mice, respectively, P<0.05) and eNOS expression were increased in KO compared to WT mice. The inhibition of eNOS with L-NAME significantly decreased endothelium response to shear stress, which was more pronounced in KO mice resistance arteries (-26.83+/-2.5 vs. -15.84+/-2.3 at 10 microl/min in KO and WT, respectively, P<0.05). However, the relaxation to exogenous nitric oxide-donor was similar in both groups.


CONCLUSIONS
Our study provides evidence of a selective effect of MMP-9 on endothelium function. Thus, MMP-9 gene deletion specifically increased resistance artery dilation endothelium-dependent and eNOS expression. Based on our results, MMP-9 could be a potential therapeutic target in cardiovascular disease associated with resistance arteries dysfunction.
Su
Jun
J
Department of Pharmacology, LSU Health Sciences Center, 1901 Perdido Street, New Orleans, LA 70112, USA.
Palen
Desiree I
DI
Lucchesi
Pamela A
PA
Matrougui
Khalid
K
D000818:Animals; D001783:Blood Flow Velocity / Q000502:physiology*; D001794:Blood Pressure / Q000502:physiology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008638:Mesenteric Arteries / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D033081:Shear Strength; D014655:Vascular Resistance / Q000235:genetics*
D061965:Matrix Metalloproteinase Inhibitors; D020780:Matrix Metalloproteinase 9