Title | Hypoxia-inducible factor-1α in vascular smooth muscle regulates blood pressure homeostasis through a peroxisome proliferator-activated receptor-γ-angiotensin II receptor type 1 axis. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Huang Y, Di Lorenzo A, Jiang W, Cantalupo A, Sessa WC, Giordano FJ |
Journal | Hypertension |
Volume | 62 |
Issue | 3 |
Pagination | 634-40 |
Date Published | 2013 Sep |
ISSN | 1524-4563 |
Keywords | Angiotensin II, Angiotensin II Type 1 Receptor Blockers, Animals, Benzimidazoles, Benzoates, Blood Pressure, Hypoxia-Inducible Factor 1, alpha Subunit, Mesenteric Arteries, Mice, Mice, Knockout, Muscle, Smooth, Vascular, PPAR gamma, Receptor, Angiotensin, Type 1, Signal Transduction, Telmisartan |
Abstract | Hypertension is a major worldwide health issue for which only a small proportion of cases have a known mechanistic pathogenesis. Of the defined causes, none have been directly linked to heightened vasoconstrictor responsiveness, despite the fact that vasomotor tone in resistance vessels is a fundamental determinant of blood pressure. Here, we reported a previously undescribed role for smooth muscle hypoxia-inducible factor-1α (HIF-1α) in controlling blood pressure homeostasis. The lack of HIF-1α in smooth muscle caused hypertension in vivo and hyperresponsiveness of resistance vessels to angiotensin II stimulation ex vivo. These data correlated with an increased expression of angiotensin II receptor type I in the vasculature. Specifically, we show that HIF-1α, through peroxisome proliferator-activated receptor-γ, reciprocally defined angiotensin II receptor type I levels in the vessel wall. Indeed, pharmacological blockade of angiotensin II receptor type I by telmisartan abolished the hypertensive phenotype in smooth muscle cell-HIF-1α-KO mice. These data revealed a determinant role of a smooth muscle HIF-1α/peroxisome proliferator-activated receptor-γ/angiotensin II receptor type I axis in controlling vasomotor responsiveness and highlighted an important pathway, the alterations of which may be critical in a variety of hypertensive-based clinical settings. |
DOI | 10.1161/HYPERTENSIONAHA.111.00160 |
Alternate Journal | Hypertension |
PubMed ID | 23918749 |
PubMed Central ID | PMC4354705 |
Grant List | HL075616-02 / HL / NHLBI NIH HHS / United States HL64001 / HL / NHLBI NIH HHS / United States |
Related Lab:
Related Faculty:
Annarita Di Lorenzo, Ph.D.