Journal article
Smooth Muscle Cell-Specific Disruption of the BBSome Causes Vascular Dysfunction
Hypertension (Dallas, Tex. 1979), Vol.74(4), pp.817-825
10/2019
DOI: 10.1161/HYPERTENSIONAHA.119.13382
PMCID: PMC6739154
PMID: 31422694
Abstract
The BBSome-a complex consisting of 8 Bardet-Biedl syndrome proteins-is involved in the regulation of various cellular processes. Recently, the BBSome complex has emerged as an important regulator of cardiovascular function with implications for disease. In this study, we examined the role of the BBSome in vascular smooth muscle and its effects on the regulation of cardiovascular function. Smooth muscle-specific disruption of the BBSome through tamoxifen-inducible deletion of
gene-a critical component of the BBSome complex-reduces relaxation and enhances contractility of vascular rings and increases aortic stiffness independent of changes in arterial blood pressure. Mechanistically, we demonstrate that smooth muscle
gene deletion increases vascular angiotensinogen gene expression implicating the renin-angiotensin system in these altered cardiovascular responses. Additionally, we report that smooth muscle-specific Bbs1 knockout mice demonstrate enhanced ET-1 (endothelin-1)-induced contractility of mesenteric arteries-an effect reversed by blockade of the AT1 (angiotensin type 1 receptor) with losartan. These findings highlight the importance of the smooth muscle BBSome in the control of vascular function and arterial stiffness through modulation of renin-angiotensin system signaling.
Details
- Title: Subtitle
- Smooth Muscle Cell-Specific Disruption of the BBSome Causes Vascular Dysfunction
- Creators
- John J Reho - From the Department of Pharmacology (J.J.R., D.-F.G., D.A.M., K.R.), University of Iowa Carver College of MedicineDeng-Fu Guo - From the Department of Pharmacology (J.J.R., D.-F.G., D.A.M., K.R.), University of Iowa Carver College of MedicineDonald A Morgan - From the Department of Pharmacology (J.J.R., D.-F.G., D.A.M., K.R.), University of Iowa Carver College of MedicineKamal Rahmouni - Veterans Affairs Health Care System, Iowa City, IA (K.R.)
- Resource Type
- Journal article
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.74(4), pp.817-825
- Publisher
- United States
- DOI
- 10.1161/HYPERTENSIONAHA.119.13382
- PMID
- 31422694
- PMCID
- PMC6739154
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Grant note
- P01 HL084207 / NHLBI NIH HHS I01 BX004249 / BLRD VA
- Language
- English
- Date published
- 10/2019
- Academic Unit
- Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984070508002771
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