Circulating microparticles and endothelial progenitor cells in atherosclerosis: pharmacological effects of irbesartan.
OBJECTIVE
This study aimed to (i) employ our newly designed model, the hypertensive-hypercholesterolemic hamster (HH), in order to find out whether a correlation exists between circulating microparticles (MPs), endothelial progenitor cells (EPCs) and their contribution to vascular dysfunction and (ii) to assess the effect of irbesartan treatment on HH animals (HHI).


RESULTS
The results showed that compared with the control (C) group, HH displayed: (i) a significant increase in plasma cholesterol and triglyceride concentration, and an augmentation of systolic and diastolic arterial blood pressure, and of heart rate; (ii) a marked elevation of MPs and a significant decrease in EPCs; (iii) structural modifications of the arterial wall correlated with altered protein expression of MMP2, MMP9, MMP12, TIMP1, TIMP2 and collagen type I and III; (iv) a considerably altered reactivity of the arterial wall closely correlated with MPs and EPC adherence; and (v) an inflammatory process characterized by augmented expression of P-Selectin, E-Selectin, von Willebrand factor, tissue factor, IL-6, MCP-1 and RANTES. Additionally, the experiments showed the potential of irbesartan to correct all altered parameters in HH and to mobilize EPCs by NO, chemokines and adhesion molecule-dependent mechanisms.


CONCLUSIONS
Hypertension associated with hypercholesterolemia is accompanied by structural modifications and expression of pro-inflammatory molecules by the vessel wall, the alteration of vascular tone, enhanced release of MPs and reduced EPCs; the ratio between the latter two may be considered as a marker of vascular dysfunction. Irbesartan, which exhibits a pharmacological control on the levels of MPs and EPCs, has the potential to restore homeostasis of the arterial wall.
Petru Poni' Institute of Macromolecular Chemistry, Iasi, Romania. adriana.georgescu@icbp.ro
A
A
Georgescu
N
N
Alexandru
E
E
Andrei
I
I
Titorencu
E
E
Dragan
C
C
Tarziu
S
S
Ghiorghe
E
E
Badila
D
D
Bartos
D
D
Popov
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D055252:Cell-Derived Microparticles / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D006224:Cricetinae; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D024022:Fibrillar Collagens / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D000077405:Irbesartan; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008647:Mesocricetus; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013777:Tetrazoles / Q000494:pharmacology*; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D024022:Fibrillar Collagens; D018836:Inflammation Mediators; D013777:Tetrazoles; D019714:Tissue Inhibitor of Metalloproteinases; D014280:Triglycerides; D002784:Cholesterol; D020782:Matrix Metalloproteinases; D000077405:Irbesartan