Effects of adrenomedullin on cell proliferation in rat adventitia induced by lysophosphatidic acid.
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.
Yang
Jing-Hui
JH
Institute of Cardiovascular Disease, Peking University First Hospital, Beijing 100034, China.
Jiang
Wei
W
Pan
Chun-Shui
CS
Qi
Yong-Feng
YF
Wu
Qi-Zhuan
QZ
Pang
Yong-Zheng
YZ
Tang
Chao-Shu
CS
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
D008246:Lysophospholipids; D010455:Peptides; D053607:Adrenomedullin; D004247:DNA; D000242:Cyclic AMP; D020928:Mitogen-Activated Protein Kinases; C032881:lysophosphatidic acid