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


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.


CONCLUSIONS
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.
Link
Andreas
A
Klinik für Innere Medizin III, Universität des Saarlandes, Homburg/Saar, Germany. link@med-in.uni-saarland.de
Lenz
Monika
M
Legner
Dominik
D
Böhm
Michael
M
Nickenig
Georg
G
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D002097:C-Reactive Protein / Q000096:biosynthesis; D018821:CD18 Antigens / Q000096:biosynthesis*; D002448:Cell Adhesion; D004311:Double-Blind Method; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000097:blood; D008214:Lymphocytes / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012084:Renin-Angiotensin System; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D000077333:Telmisartan
D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001565:Benzoates; D018821:CD18 Antigens; D015850:Interleukin-6; D016177:Macrophage-1 Antigen; D002097:C-Reactive Protein; D000077333:Telmisartan