Small artery remodeling depends on tissue-type transglutaminase.
Remodeling of small arteries is essential in the long-term regulation of blood pressure and blood flow to specific organs or tissues. A large part of the change in vessel diameter may occur through non-growth-related reorganization of vessel wall components. The hypothesis was tested that tissue-type transglutaminase (tTG), a cross-linking enzyme, contributes to the inward remodeling of small arteries. The in vivo inward remodeling of rat mesenteric arteries, induced by low blood flow, was attenuated by inhibition of tTG. Rat skeletal muscle arteries expressed tTG, as identified by Western blot and immunostaining. In vitro, activation of these arteries with endothelin-1 resulted in inward remodeling, which was blocked by tTG inhibitors. Small arteries obtained from rats and pigs both showed inward remodeling after exposure to exogenous transglutaminase, which was inhibited by addition of a nitric oxide donor. Enhanced expression of tTG, induced by retinoic acid, increased inward remodeling of porcine coronary arteries kept in organ culture for 3 days. The activity of tTG was dependent on pressure. Inhibition of tTG reversed remodeling, causing a substantial increase in vessel diameter. In a collagen gel contraction assay, tTG determined the compaction of collagen by smooth muscle cells. Collectively, these data show that small artery remodeling associated with chronic vasoconstriction depends on tissue-type transglutaminase. This mechanism may reveal a novel therapeutic target for pathologies associated with inward remodeling of the resistance arteries.
Bakker
Erik N T P
EN
Department of Medical Physics, Academic Medical Center and Cardiovascular Research Institute Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands. n.t.bakker@amc.uva.nl
Buus
Carsten L
CL
Spaan
Jos A E
JA
Perree
Jop
J
Ganga
Anuradha
A
Rolf
Titia M
TM
Sorop
Oana
O
Bramsen
Linda H
LH
Mulvany
Michael J
MJ
Vanbavel
Ed
E
D000588:Amines / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000201:enzymology; D001710:Biotin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002103:Cadaverine / Q000494:pharmacology; D048429:Cell Size / Q000187:drug effects; D003094:Collagen; D003331:Coronary Vessels / Q000166:cytology; D003432:Cross-Linking Reagents / Q000494:pharmacology; D003538:Cystamine / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D005109:Extracellular Matrix / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000187:drug effects; D005260:Female; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D005782:Gels; D006168:Guinea Pigs; D018056:Hemorheology; D008638:Mesenteric Arteries / Q000201:enzymology / Q000502:physiology*; D018482:Muscle, Skeletal / Q000098:blood supply; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D009569:Nitric Oxide / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D009924:Organ Culture Techniques; D010208:Papaverine / Q000494:pharmacology; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D051381:Rats; D034421:Sus scrofa; D011503:Transglutaminases / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D014212:Tretinoin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014666:Vasomotor System / Q000502:physiology*
D000588:Amines; D003432:Cross-Linking Reagents; D019332:Endothelin-1; D016326:Extracellular Matrix Proteins; D005782:Gels; D020030:Nitric Oxide Donors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C076022:5-(biotinamido)pentylamine; D009599:Nitroprusside; D009569:Nitric Oxide; D014212:Tretinoin; D001710:Biotin; D003094:Collagen; D010208:Papaverine; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins; D002103:Cadaverine; D003538:Cystamine; D009638:Norepinephrine