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.
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Emerging evidence indicates that adding a statin to angiotensin II system inhibition or AT-1 receptor blockade yields greater improvements in endothelial dysfunction, inflammation, and oxidative stress.
“On the other hand, evidence for the possibility of obtaining a more marked effect on endothelial dysfunction, inflammation, and oxidative stress by combining statins with the inhibition of angiotensin II system or blocking AT-1 recep- tors is emerging.[41][42][43][44]”
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- Authors
- Nomura, S., Shouzu, A., Omoto, S., Nishikawa, M., & Iwasaka, T.
- Affiliations
- Kansai Medical University (JP)
- Venue
- Clinical and Applied Thrombosis/Hemostasis
- Publisher
- SAGE Publications
- Published
- 2004-04
- Volume
- 10
- Issue
- 2
- Pages
- 133-141
- ISSN
- 1076-0296 (ISSN-L)
- 1938-2723
- OpenAlex
- W2100471336
- Cited by
- 87
- References
- 55
- Citations by year
- 2024: 2 · 2022: 7 · 2021: 4 · 2020: 6 · 2019: 2 · 2018: 4 · 2017: 3 · 2016: 6 · 2015: 5 · 2014: 5 · 2013: 6 · 2012: 6
- FWCI
- 1.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical and Applied Thrombosis/Hemostasis (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- losartan, simvastatin, monocyte-derived microparticles, type 2 diabetes, hypertension, angiotensin receptor blockers, statin combination therapy, diabetic vascular disease, atherosclerosis, chemokines, MCP-1, RANTES, soluble adhesion molecules, soluble P-selectin, sVCAM-1, blood pressure reduction, diabetic nephropathy
- MeSH terms
- Aged, Blood Pressure, Diabetes Mellitus, Female, Humans, Hypertension, Male, Middle Aged, Monocytes, Receptors, Angiotensin, Biomarkers, Chemokines, Losartan, Simvastatin, Diabetes Complications, Angiotensin Receptor Antagonists
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