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Apelin regulation of potassium chloride cotransport (KCC) in vascular smooth muscle cells (VSMCs): Relation to Cardiovascular Disease (CVD)
Author(s) -
Sharma Neelima,
Lauf Peter K,
Adragorma C
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.736.5
Subject(s) - apelin , vascular smooth muscle , endocrinology , signal transduction , mapk/erk pathway , medicine , pi3k/akt/mtor pathway , protein kinase b , microbiology and biotechnology , receptor , chemistry , biology , smooth muscle
Apelin, a potent inodilator, uses the NO pathway to elicit its anti‐atherogenic effect, and the PI3K/Akt and MAPK pathways to induce proliferation and migration of VSMCs. The NO pathway is predominant in healthy blood vessels and contractile VSMCs, whereas, the PI3K/Akt/MAPK pathways are prominent in diseased blood vessels and secretory VSMCs. VSMCs participate in atherosclerotic lesions due to their capacity to migrate and proliferate. Oxidized plasma cholesterol (oxLDL) is a detrimental factor in atheroma formation. It is known that KCC uses the same regulatory pathways (Adragna et al. 2006) as apelin and is implicated in CVD. Here, we tested the hypothesis that apelin through its APJ receptor signaling pathways regulates KCC. Expression and distribution patterns of contractile proteins were studied by Western blot and immunofluorescence. KCC activity was measured by atomic absorption spectrophotometry with Rb as K congener ± inhibitors of the aforementioned signaling pathways and by blocking other K + transport mechanisms. The APJ receptor and key components of the signaling pathways were verified immunologically. VSMCs’ identity was established by appropriate markers. Apelin stimulated KCC activity through the NO pathway by 335 % and by 142 % through the MAPK/PI3K pathways, In contrast, oxLDL inhibited baseline KCC in contractile VSMCs, and this inhibition was restored by apelin. These findings prove the hypothesis that apelin regulates KCC activity through the aforementioned pathways, are relevant to CVD and have potential as therapeutic targets. Supported by WSU Foundation.