L-type calcium channel blockers exert an antiinflammatory effect by suppressing expression of plasminogen receptors on macrophages.

Abstract:

:L-type Ca(2+) channel (LTCC) blockers, represented by amlodipine and verapamil, are widely used antihypertensive drugs that also have antiinflammatory activities. Plasminogen (Plg) is an important mediator of macrophage recruitment, and this role depends on its interaction with Plg receptors (Plg-Rs). Plg-Rs include histone 2B, alpha-enolase, annexin 2, and p11, all proteins which lack signal sequences for cell surface export. When human or murine monocytoid cells were induced to differentiate into macrophages, their Plg binding and Plg-R expression increased by 4-fold. These changes were suppressed by pretreatment with verapamil and amlodipine. Expression of the Ca(v)1.2 LTCC pore subunit was induced in differentiated macrophages, and siRNA against this subunit suppressed the upregulation of Plg binding and Plg-Rs. In vivo, amlodipine and verapamil suppressed peritoneal macrophage recruitment in response to thioglycollate by >60% at doses that did not affect blood pressure. In drug-treated animals, macrophages migrated into but not through the peritoneal membrane tissue and showed reduced surface expression of Plg-Rs. These findings demonstrate that Plg-R expression on macrophages is dependent on Ca(v)1.2 LTCC subunit expression. Suppression of Plg-Rs may contribute to the antiinflammatory effects of the widely used LTCC blockers.

journal_name

Circ Res

journal_title

Circulation research

authors

Das R,Burke T,Van Wagoner DR,Plow EF

doi

10.1161/CIRCRESAHA.109.200311

subject

Has Abstract

pub_date

2009-07-17 00:00:00

pages

167-75

issue

2

eissn

0009-7330

issn

1524-4571

pii

CIRCRESAHA.109.200311

journal_volume

105

pub_type

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