title: Myosin phosphatase isoforms and related transcripts in the pig coronary circulation and effects of exercise and chronic occlusion.
abstract: Myosin phosphatase (MP) is a key target of signaling pathways that regulate smooth muscle tone and blood flow. Alternative splicing of MP targeting subunit (MYPT1) exon 24 (E24) generates isoforms with variable presence of a C-terminal leucine zipper (LZ) required for activation of MP by NO/cGMP. Here we examined the expression of MP and associated genes in a disease model in the coronary circulation. Female Yucatan miniature swine remained sedentary or were exercise-trained beginning eight weeks after placement of an ameroid constrictor around the left circumflex (LCX) artery. Fourteen weeks later epicardial arteries (~1mm) and resistance arterioles (~125 μm) were harvested and assayed for gene expression. MYPT1 isoforms were distinct in the epicardial arteries (E24-/LZ+) and resistance arterioles (E24+/LZ-) and unchanged by exercise training or coronary occlusion. MYPT1, CPI-17 and PDE5 mRNA levels were not different between arteries and arterioles while Kir2.1 and eNOS were 6.6-fold and 3.9-fold higher in the arterioles. There were no significant changes in transcript abundance in epicardial arteries of the collateralized (LCX) vs. non-occluded left anterior descending (LAD) territories, or in exercise-trained vs. sedentary pigs. There was a significant 1.2 fold increase in CPI-17 in collateral-dependent arterioles, independent of exercise, and a significant 1.7 fold increase in PDE5 in arterioles from exercise-trained pigs, independent of occlusion. We conclude that differences in MYPT1 E24 (LZ) isoforms, eNOS, and Kir2.1 distinguish epicardial arteries and resistance coronary arterioles. Up-regulation of coronary arteriolar PDE5 by exercise and CPI-17 by chronic occlusion could contribute to altered vasomotor responses and requires further study.
authors.affiliation: Division of Cardiology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA.
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Physiology and Pharmacology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Cristine L
authors.initials: CL
authors.lastname: Heaps
authors.affiliation: Division of Cardiology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA. Electronic address: sfisher1@medicine.umaryland.edu.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Fisher
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001160:Arterioles / Q000378:metabolism; D001483:Base Sequence; D003326:Coronary Circulation; D054059:Coronary Occlusion / Q000201:enzymology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D043263:Myosin-Light-Chain Phosphatase / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D013552:Swine; D013556:Swine, Miniature
chemical_list: D007527:Isoenzymes; D043263:Myosin-Light-Chain Phosphatase