No and neurogulins: Autacoid signaling in the heart

Abstract

AS in other organs and tissues, the heart utilizes a number of autocrine, paracrine, and juxtacrine (autacoid) signaling pathways to respond both to moment-to-moment changes in demand and to longer term adaptation to physiologic stress, including (among others) nitric oxide (NO) and neuregulins. Aside from endothelium, NO within the heart is also produced by the NO synthase “eNOS” in atrial and ventricular myocytes, including SA and AV nodal cells, where it activates guanylyl cyclase in response to m2 muscarinic and purinergic agonists. Both coronary microvascular endothelial cells (CMEC) and cardiac myocytes also express inducible NOS (iNOS), a principal effector of “innate immunity”, in response to intracardiac inflammatory cytokines. CMEC, including capillary and venular endothelium, express a number of peptide autacoids, including angiotensins and endothelins, and also neuregulinI (NRGI), a family of autacoids essential for normal ventricular development. Cardiac myocytes, which express the neuregulin receptors erbB2, erbB3, and erbB4 during development, continue to express erbB4 (and, to a lesser extent erbB2) in the postnatal myocardium. An improved understanding of the complexity of autacoid signaling in the postnatal and adult myocardium will enable the development of new therapeutic strategies and targets for the stressed myocardium.