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Contrasting vascular effects caused by loss of Bardet-Biedl syndrome genes
Journal article   Open access   Peer reviewed

Contrasting vascular effects caused by loss of Bardet-Biedl syndrome genes

Andreas M Beyer, Deng-Fu Guo, Val C Sheffield and Kamal Rahmouni
American journal of physiology. Heart and circulatory physiology, Vol.299(6), pp.H1902-1907
12/2010
DOI: 10.1152/ajpheart.00336.2010
PMCID: PMC3006278
PMID: 20852044
url
https://doi.org/10.1152/ajpheart.00336.2010View
Published (Version of record) Open Access

Abstract

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous, autosomal-recessive disorder associated with several clinical features including obesity, hypertension, and cardiovascular abnormalities. BBS proteins play an important role in the function of cilia, a mechanosensory organelle in endothelial cells, but whether these proteins are directly involved in the regulation of vascular function is unclear. Here, we show that Bbs genes (1-12) are expressed in endothelial and smooth muscle cell lines and tissues enriched in endothelial (lung) and smooth muscle (stomach) cells as well as the aorta. Next, we used aortic rings to examine the vascular function of two BBS mouse models that recapitulate the human phenotype, namely Bbs2(-/-) (obese and normotensive) and Bbs6(-/-) (obese and hypertensive) mice. Interestingly, the endothelium-dependent relaxation (induced by ACh) was significantly enhanced in Bbs2(-/-) but not Bbs6(-/-) mice. In contrast, the endothelium-independent relaxation (induced by sodium nitroprusside) was unaltered in both BBS mouse models. In addition, the contractile responses to serotonin and endothelin-1 were attenuated in Bbs2(-/-) but not Bbs6(-/-) mice. Of note, the NO-producing enzymes (eNOS and iNOS) were upregulated in the aorta of Bbs2(-/-) but not Bbs6(-/-) mice. On the other hand, the expression level of membrane subunits of NADPH oxidase (p22(phox) and p47(phox)) in the aorta was decreased in Bbs2(-/-) mice but increased in Bbs6(-/-) mice. In conclusion, these data implicate Bbs genes in the regulation of vascular function and demonstrate that disrupting Bbs2 and Bbs6 genes affect differentially the vascular function.
 Bardet-Biedl Syndrome - metabolism Muscle, Smooth, Vascular - metabolism NADPH Oxidases - metabolism Endothelium, Vascular - drug effects Aorta - metabolism Muscle, Smooth, Vascular - physiopathology Obesity - genetics Dose-Response Relationship, Drug Group II Chaperonins - genetics Bardet-Biedl Syndrome - genetics Aorta - physiopathology Hypertension - genetics Nitric Oxide Synthase Type III - metabolism Muscle, Smooth, Vascular - drug effects Vasoconstrictor Agents - pharmacology Cell Line Vasodilator Agents - pharmacology Group II Chaperonins - deficiency Stomach - blood supply Endothelium, Vascular - physiopathology Genotype Obesity - physiopathology Bardet-Biedl Syndrome - physiopathology Vasoconstriction - drug effects Hypertension - physiopathology Hypertension - metabolism Mice, Knockout Obesity - metabolism Proteins - genetics Phenotype Animals Proteins - metabolism Endothelium, Vascular - metabolism Mice Vasodilation - drug effects Lung - blood supply Nitric Oxide - metabolism Nitric Oxide Synthase Type II - metabolism

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