BACKGROUND: Arterial stiffness (AS), or loss of elastic compliance of large arteries, is an independent risk factor for cardiovascular events1. A recent study demonstrated that single nucleotide polymorphisms (SNPs) in a genetic locus downstream of the gene Bcl11b are associated with AS2. However, how this genetic locus and Bcl11b regulate AS is unknown.
OBJECTIVES: To determine the molecular mechanisms by which Bcl11b effects the aortic wall and AS.
METHODS: Vascular smooth muscle (VSM) cells were isolated from aortas of wildtype (WT) mice and mice with VSM-specific Bcl11b deletion (BKO). mRNA levels of Bcl11b, vascular contractile markers (myosin heavy chain 11 (MYH11), smooth muscle -actin (ACTA2), and myocardin (MYOCD)) and a cell proliferation marker (Ki67) were measured in WT and BKO VSM cells isolated from murine aortas. VSM cell contractility in response to angiotensin II (angII), a contractile stimulus, was measured in WT and BKO VSM cells using an optimized collagen gel contractility assay.
RESULTS: BKO VSM cells had decreased expression of contractile markers compared to WT cells, which resulted in impaired collagen gel contraction in response to angII.
CONCLUSIONS: Bc111b is expressed in aortic smooth muscle cells and it regulates the expression of VSM contractile proteins. Our data strongly supports the hypothesis that Bcl11b regulates AS by regulating the contractile function of VSM cells in the aortic wall. / 2019-07-11T00:00:00Z
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/23716 |
| Date | 11 July 2017 |
| Creators | Elavalakanar, Pavania |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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