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.
Department of Medicine, Baylor College of Medicine, 6550 Fannin, SM MS 1423, Houston, TX 77030, USA.
D A
DA
Tulis
W
W
Durante
K J
KJ
Peyton
A J
AJ
Evans
A I
AI
Schafer
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