title: Protein kinase C alpha modulates microvascular reactivity in the human coronary and skeletal microcirculation.
abstract: BACKGROUND
  Cardioplegic arrest (CP) and cardiopulmonary bypass (CPB) can lead to dysfunction in the coronary and skeletal microcirculation leading to impaired tissue perfusion. alpha-Adrenergic signaling pathways acting on these microcirculatory beds are thought to involve protein kinase C (PKC). We investigate here the role of the conventional PKCs in microvascular function in the setting of CP/CPB.
  
  
  METHODS
  Atrial and skeletal muscle was harvested from 30 patients undergoing cardiac surgery before and after CP/CPB. Microvessels were used for Western blotting and immunofluorescent staining against conventional PKCs. Microvascular constriction was assessed in pre- and post-CP/CPB samples in response to alpha-adrenergic stimulation with phenylephrine, with and without a PKC-alpha inhibitor or PKC-alpha activator. PKC activity was assessed in isolated microvessels.
  
  
  RESULTS
  Western blotting and immunostaining demonstrated only PKC-alpha in coronary and skeletal microvessels. CP/CPB diminished contractile responses to phenylephrine in coronary and skeletal samples. Inhibition of PKC-alpha reduced phenylephrine induced vasoconstriction in coronary and skeletal microvessels, whereas activation of PKC-alpha-augmented phenylephrine induced responses. PKC activity was decreased in coronary microvessels and to an even greater degree in skeletal microvessels after CP/CPB.
  
  
  CONCLUSIONS
  PKC-alpha is the predominant conventional PKC present in the human coronary and skeletal microcirculation. It likely plays a key role in alpha-adrenergic signaling in microvessels and in the vasomotor dysfunction after CP/CPB.
authors: Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass, USA.
authors: Neel R
authors: NR
authors: Sodha
authors: Jun
authors: J
authors: Feng
authors: Richard T
authors: RT
authors: Clements
authors: Cesario
authors: C
authors: Bianchi
authors: Munir
authors: M
authors: Boodhwani
authors: Basel
authors: B
authors: Ramlawi
authors: Shigetoshi
authors: S
authors: Mieno
authors: Kamal R
authors: KR
authors: Khabbaz
authors: Frank W
authors: FW
authors: Sellke
mesh_terms: D000368:Aged; D015153:Blotting, Western; D002196:Capillaries / Q000201:enzymology*; D003326:Coronary Circulation / Q000502:physiology*; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000502:physiology; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply*; D009206:Myocardium; D011493:Protein Kinase C / Q000378:metabolism; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D014661:Vasoconstriction / Q000502:physiology
chemical_list: C087857:protein kinase C gamma; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha