title: Effects of losartan and simvastatin on monocyte-derived microparticles in hypertensive patients with and without type 2 diabetes mellitus.
abstract: Monocyte-derived microparticles play an important role in the pathogenesis of diabetic vasculopathy, and angiotensin II receptor blocker and statin have been shown to have a beneficial effect on the angiopathies of hypertension and hyperglycemia in patients with type 2 diabetes mellitus. However, the interaction between angiotensin II receptor blocker and statin, and monocyte-derived microparticles in atherosclerosis is poorly understood. The effects of losartan and simvastatin on circulating concentrations of monocyte-derived microparticles, chemokines, and soluble adhesion markers were studied in hypertensive patients with or without type 2 diabetes mellitus. Monocyte-derived microparticles were measured by flow cytometry, and levels of serum chemokines (MCP-1 and RANTES) and soluble adhesion markers (sP-selectin and sVCAM-1) were measured by enzyme-linked immunosorbent assay. Losartan decreased both the systolic and diastolic blood pressure in hypertensive patients with and without type 2 diabetes mellitus. The concentrations of monocyte-derived microparticles, chemokines, and soluble adhesion molecules were higher in hypertensive patients who also had type 2 diabetes mellitus vs. those who did not. The administration of angiotensin II receptor blocker decreased the circulating concentration of all these markers. In addition, all markers were decreased by combination therapy, and monocyte-derived microparticles were decreased more with combination therapy with losartan and simvastatin than monotherapy with losartan. The administration of angiotensin II receptor blocker inhibited monocyte-derived microparticle generation and suggests that angiotensin II is intimately related to vascular changes that occur in type 2 diabetes mellitus. Combination therapy with a statin and angiotensin II receptor blocker might be valuable as anti-atherosclerotic therapy in patients with type 2 diabetes mellitus and nephropathy.
authors.affiliation: First Department of Internal Medicine, Kansai Medical University, Osaka, Japan. shosaku-n@mbp.ocn.ne.jp
authors.forename: Shosaku
authors.initials: S
authors.lastname: Nomura
authors.forename: Akira
authors.initials: A
authors.lastname: Shouzu
authors.forename: Seitaro
authors.initials: S
authors.lastname: Omoto
authors.forename: Mitsushige
authors.initials: M
authors.lastname: Nishikawa
authors.forename: Toshiji
authors.initials: T
authors.lastname: Iwasaka
mesh_terms: D000368:Aged; D057911:Angiotensin Receptor Antagonists; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D018925:Chemokines / Q000097:blood; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000188:drug therapy*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy*; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000378:metabolism; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D057911:Angiotensin Receptor Antagonists; D015415:Biomarkers; D018925:Chemokines; D011945:Receptors, Angiotensin; D019821:Simvastatin; D019808:Losartan