Telmisartan inhibits beta2-integrin MAC-1 expression in human T-lymphocytes.

Abstract:

OBJECTIVE:The pathogenesis of atherosclerosis, a chronic inflammatory disease, is influenced by the renin-angiotensin system and especially by angiotensin II subtype 1 (AT1) receptor activation. Although pro-inflammatory properties of angiotensin II as well as anti-inflammatory effects of AT1 receptor antagonists are well known, the underlying mechanisms are poorly understood. METHOD AND RESULTS:In a prospective double-blind study, patients with hypertension and coronary artery disease were treated with either 40 mg telmisartan (n = 21) or placebo (n = 21) for 12 weeks. General markers of inflammation, such as high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6), and cell adhesion molecules, such as soluble intercellular adhesion molecule (s-ICAM-1) and the leucocyte adhesion molecule soluble-L-selectin (sL-selectin), as well as the lymphocytic expression of the beta2 integrin MAC-1, were assessed before and after treatment. Telmisartan therapy significantly decreased the lymphocyte beta2 integrin MAC-1 expression, whereas hs-CRP, IL-6, s-ICAM and sL-selectin remained unaltered. In-vitro experiments were conducted to clarify the mode of action. Cultured human lymphocytes were stimulated with either angiotensin II or phorbol-12-myristate-13-acetate (PMA)/ionomycin, alone or after pretreatment with telmisartan. Whereas angiotensin II exerted no effect on beta2-integrin MAC-1 expression in lymphocytes, telmisartan dose-dependently inhibited beta2-integrin expression in lymphocytes in the absence or presence of angiotensin II. CONCLUSION:The AT1 receptor antagonist telmisartan inhibits the expression of the pro-inflammatory beta2-integrin MAC-1 expression in lymphocytes independently of angiotensin II, suggesting an AT1 receptor-independent atheroprotective effect of this AT1 receptor antagonist.

journal_name

J Hypertens

journal_title

Journal of hypertension

authors

Link A,Lenz M,Legner D,Böhm M,Nickenig G

doi

10.1097/01.hjh.0000242415.73406.17

subject

Has Abstract

pub_date

2006-09-01 00:00:00

pages

1891-8

issue

9

eissn

0263-6352

issn

1473-5598

pii

00004872-200609000-00029

journal_volume

24

pub_type

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