title: Enzymatic changes in myosin regulatory proteins may explain vasoplegia in terminally ill patients with sepsis.
abstract: The current study was conducted with the hypothesis that failure of maintenance of the vascular tone may be central to failure of the peripheral circulation and spiralling down of blood pressure in sepsis. Namely, we examined the balance between expression of myosin light chain (MLC) phosphatase and kinase, enzymes that regulate MLCs dephosphorylation and phosphorylation with a direct effect on pharmacomechanical coupling for smooth muscle relaxation and contraction respectively. Mechanical recordings and enzyme immunoassays of vascular smooth muscle lysates were used as the major methods to examine arterial biopsy samples from terminally ill sepsis patients. The results of the present study provide evidence that genomic alteration of expression of key regulatory proteins in vascular smooth muscles may be responsible for the relentless downhill course in sepsis. Down-regulation of myosin light chain kinase (MLCK) and up-regulation of MLCK may explain the loss of tone and failure to mount contractile response in vivo during circulation. The mechanical studies demonstrated the inability of the arteries to develop tone when stimulated by phenylephrine in vitro. The results of our study provide indirect hint that control of inflammation is a major therapeutic approach in sepsis, and may facilitate to ameliorate the progressive cardiovascular collapse.
authors.affiliation: Incentive Care Unit, Binzhou People Hospital, Shandong, Binzhou 256600, China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Cardiovascular Medicine, Binzhou People Hospital, Shandong, Binzhou 256600, China ky7171@aliyun.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Kou
authors.affiliation: Department of Nephrology, Binzhou People Hospital, Shandong, Binzhou 256600, China.
authors.forename: Feng-lan
authors.initials: FL
authors.lastname: Gao
authors.affiliation: Incentive Care Unit, Binzhou People Hospital, Shandong, Binzhou 256600, China.
authors.forename: Xiu-he
authors.initials: XH
authors.lastname: Ouyang
mesh_terms: D000368:Aged; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism* / Q000473:pathology; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism*; D018805:Sepsis / Q000378:metabolism*; D019452:Terminally Ill; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D056987:Vasoplegia / Q000378:metabolism* / Q000473:pathology
chemical_list: C403126:MYLIP protein, human; D044767:Ubiquitin-Protein Ligases; D009219:Myosin-Light-Chain Kinase
keywords: cardiocirculatory collapse; myosin light chain kinase (MLCK); pharmacomechanical coupling; sepsis