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Microvascular Smooth Muscle Gene Program is Highly Sensitive to Blood Flow
Author(s) -
Reho John J,
Fisher Steven A
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.924.12
Subject(s) - gene isoform , medicine , biology , blood flow , pulsatile flow , alternative splicing , myosin light chain phosphatase , cardiology , anatomy , myosin , microbiology and biotechnology , myosin light chain kinase , gene , biochemistry
Microvascular smooth muscle (MVSM) is phenotypically and functionally distinct from that of the large arteries yet the deterministic input signals are not known. We use Myosin Phosphatase as a model to address this question as it is a primary mediator of vasomotor responses. Isoforms of the myosin phosphatase regulatory subunit (Mypt1) are generated by alternative splicing of exon 24 (E24) and determine MVSM responses to NO/cGMP. Mesenteric artery MVSM expresses the E24+ (fast) isoform; large arteries express the E24‐ (slow) isoform. Ligation of the downstream MA2s causes switching of the upstream MA1s to the E24‐ isoform suggesting the hypothesis that the unique (fast) contractile phenotype of MVSM is determined by blood flow. To test this we developed a model of reduced perfusion pressure in which placement of an occluder around the abdominal aorta allows for transient reductions in blood flow within the rat mesenteric arcade. Brief (20 & 60min) and repetitive (60min; 5days) perfusion pressure reduction via the balloon occluder causes a switch in the splicing of E24 in Mypt1 of mesenteric arteries from the E24+ to E24‐ isoform 6 hours after pressure reduction in both brief (20% E24+ vs 80% control; p<0.05) and repetitive (45% E24+; p<0.05) protocols. Given these effects of reduced perfusion pressure we propose that the unique properties of the MVSM are highly dependent upon the pulsatile blood flow generated by the heart