Heme oxygenase-1 attenuates vascular remodeling following balloon injury in rat carotid arteries.
The heme oxygenase-1 (HO-1) system of heme catabolism has been proposed to exert protective actions upon the cardiovascular system. This investigation examined the influence of HO-1 induction on vascular remodeling following arterial injury. Rats were subjected to left carotid artery (LCA) balloon injury following pre-treatment with either vehicle, the HO-1 inducer hemin (50 mg/kg, SC), or concomitant treatment with hemin and the HO-1 inhibitor tin-protoporphyrin IX (SnPP-IX; 50 micromol/kg, IP). Animals were injected daily for 14 days post-injury, after which animals were sacrificed and tissues obtained. Western blot analyses revealed vascular HO-1 induction after 2 and 16 days of hemin treatment. Positive immunostaining for HO-1 was detected in the endothelial and adventitial layers following 48 h of hemin treatment and positive medial staining for HO-1 after 16 days of hemin treatment. The injured LCA of hemin-treated animals demonstrated significantly attenuated neointimal (NI) area (-57%), NI thickness (-58%), and NI area/medial wall area ratio (-40%) compared to the injured LCA of vehicle controls. The cross-sectional medial wall areas of both LCA and uninjured RCA were also significantly reduced in the hemin-treated animals. SnPP-IX treatment, however, completely restored the NI area, NI thickness, NI area/medial wall area ratio, and partially restored the medial wall area towards control levels. These results directly implicate HO-1 and the products of heme catabolism in attenuating the arterial response to injury and ensuing vascular wall remodeling.
Tulis
D A
DA
Department of Medicine, Baylor College of Medicine, 6550 Fannin, SM MS 1423, Houston, TX 77030, USA.
Durante
W
W
Peyton
K J
KJ
Evans
A J
AJ
Schafer
A I
AI
D000818:Animals; D002339:Carotid Arteries / Q000473:pathology / Q000502:physiology*; D002404:Catheterization; D004730:Endothelium, Vascular / Q000473:pathology; D006419:Heme Oxygenase (Decyclizing) / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D051547:Heme Oxygenase-1; D006427:Hemin / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology
D008665:Metalloporphyrins; D011524:Protoporphyrins; D006427:Hemin; C032628:tin protoporphyrin IX; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1