Protein kinase C alpha modulates microvascular reactivity in the human coronary and skeletal microcirculation

Neel R. Sodha, Jun Feng, Richard T. Clements, Cesario Bianchi, Munir Boodhwani, Basel Ramlawi, Shigetoshi Mieno, Kamal R. Khabbaz, Frank W. Sellke

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Background: Cardioplegic arrest (CP) and cardiopulmonary bypass (CPB) can lead to dysfunction in the coronary and skeletal microcirculation leading to impaired tissue perfusion. α-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 α-adrenergic stimulation with phenylephrine, with and without a PKC-α inhibitor or PKC-α activator. PKC activity was assessed in isolated microvessels. Results: Western blotting and immunostaining demonstrated only PKC-α in coronary and skeletal microvessels. CP/CPB diminished contractile responses to phenylephrine in coronary and skeletal samples. Inhibition of PKC-α reduced phenylephrine induced vasoconstriction in coronary and skeletal microvessels, whereas activation of PKC-α-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-α is the predominant conventional PKC present in the human coronary and skeletal microcirculation. It likely plays a key role in α-adrenergic signaling in microvessels and in the vasomotor dysfunction after CP/CPB.

Original languageEnglish (US)
Pages (from-to)243-252
Number of pages10
JournalSurgery
Volume142
Issue number2
DOIs
StatePublished - Aug 1 2007

ASJC Scopus subject areas

  • Surgery

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