Contrasting vascular effects caused by loss of Bardet-Biedl syndrome genes
Open accessAbstract
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.
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Vascular defects such as endothelial dysfunction are not universally associated with obesity.
“It should be noted, however, that vascular defects such as endothelial dysfunction are not universally associated with obesity. This is based on a number of studies showing the development of obesity without concomitant presence of vascular abnormalities (65;72).”
From Obesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis (2014) · cites this paper as [72]
Mice lacking the Bardet-Biedl syndrome 2 gene do not display endothelial dysfunction despite the presence of obesity.
“For instance, mice lacking the Bardet-Biedl syndrome 2 gene do not display endothelial dysfunction despite the presence of obesity (72).”
From Obesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis (2014) · cites this paper as [72]
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- Authors
- Beyer, A. M., Guo, D.-F., Sheffield, V. C., & Rahmouni, K.
- Affiliations
- Departments of 1Internal Medicine and
- University of Iowa (US)
- Corresponding author
- Rahmouni, Kamal
- Venue
- American Journal of Physiology-Heart and Circulatory Physiology
- Publisher
- American Physiological Society
- Published
- 2010-12
- Volume
- 299
- Issue
- 6
- Pages
- H1902-H1907
- ISSN
- 0363-6135 (ISSN-L)
- 1522-1539
- PMC
- PMC3006278
- OpenAlex
- W2154165832
- Cited by
- 14
- References
- 34
- Citations by year
- 2024: 1 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 3 · 2017: 1 · 2015: 1 · 2014: 1 · 2013: 1 · 2012: 1
- FWCI
- 0.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Heart and Circulatory Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Heart, Lung, and Blood Institute (HL-07121, HL-084207, P01HL084207)
- National Eye Institute (R01EY011298)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Keywords
- Bardet-Biedl syndrome, BBS2, vascular function, endothelial cells, smooth muscle cells, aorta, endothelium-dependent relaxation, hypertension, obesity, cilia, nitric oxide synthase, NADPH oxidase, endothelin-1, serotonin
- MeSH terms
- Animals, Aorta, Cell Line, Dose-Response Relationship, Drug, Endothelium, Vascular, Genotype, Hypertension, Lung, Muscle, Smooth, Vascular, Nitric Oxide, Obesity, Phenotype, Proteins, Stomach, Vasoconstriction, Vasoconstrictor Agents, Vasodilation, Vasodilator Agents, Mice, Knockout, NADPH Oxidases, Bardet-Biedl Syndrome, Mice, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type III, Group II Chaperonins
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