title: Effects of adrenomedullin on cell proliferation in rat adventitia induced by lysophosphatidic acid.
abstract: Lysophosphatidic acid (LPA) is a bioactive phospholipid having growth factor-like activity on fibroblasts and is involved in cardiovascular diseases such as hypertension and heart failure by inducing vascular remodeling, characterized by fibroblast proliferation and migration in adventitia. Among various bioactive factors that LPA works with, adrenomedullin (ADM) is a multiple functional peptide with an important cytoprotective effect against cardiovascular damage. We studied rat aortic adventitia to explore the possible paracrine/autocrine interaction between endogenous ADM and LPA. LPA stimulation of the adventitia to secrete ADM and express its mRNA was concentration dependent. ADM inhibited LPA-induced proliferation in adventitial cells and attenuated the activity of mitogen-activated protein kinase (MAPK) stimulated by LPA. In contrast, treatment with specific antagonists of the ADM receptor potentiated the LPA-induced proliferation in adventitial cells. We concluded that LPA stimulates the adventitia to produce and secrete ADM, which in turn regulates the vascular biological effects of LPA.
authors.affiliation: Institute of Cardiovascular Disease, Peking University First Hospital, Beijing 100034, China.
authors.forename: Jing-Hui
authors.initials: JH
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Chun-Shui
authors.initials: CS
authors.lastname: Pan
authors.forename: Yong-Feng
authors.initials: YF
authors.lastname: Qi
authors.forename: Qi-Zhuan
authors.initials: QZ
authors.lastname: Wu
authors.forename: Yong-Zheng
authors.initials: YZ
authors.lastname: Pang
authors.forename: Chao-Shu
authors.initials: CS
authors.lastname: Tang
mesh_terms: D053607:Adrenomedullin; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003238:Connective Tissue / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D008246:Lysophospholipids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019899:Paracrine Communication / Q000187:drug effects; D010455:Peptides / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology* / Q000502:physiology; D051381:Rats
chemical_list: D008246:Lysophospholipids; D010455:Peptides; D053607:Adrenomedullin; D004247:DNA; D000242:Cyclic AMP; D020928:Mitogen-Activated Protein Kinases; C032881:lysophosphatidic acid