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Aim:We examined the anti-oxidant mechanisms of combined therapy of eicosapentaenoic acid (EPA) plus statin on the progression of atherosclerosis. Methods: Patients receiving statin therapy for dyslipidemia and with coronary artery disease (CAD) were assigned randomly in an open-label manner to the EPA (1,800 mg/day) -plus-statin group (n 25; combined-therapy group) or to the statin-only group (n 25), and followed for 48 weeks. At baseline and 48 weeks after enrollment, oxidative stress, brachial-ankle pulse wave velocity (baPWV) and stiffness parameter -index of the carotid were measured. Results: The lipid profile remained unchanged throughout the study. Although the median value of baPWV increased more in the statin-only group than in the combined-therapy group, this difference was not significant (p 0.29); however, a decrease in baPWV was associated with combined-therapy treatment by multiple regression analysis adjusted for age and mean blood pressure (p 0.04). In addition, the -index of the carotid was lower in the combined-therapy group than in the statin-only group (p 0.02). Furthermore, although the difference in the reduction of the urinary concentration of 8-isoprostane between the two groups did not reach statistical significance, this concentration was significantly lower in the combined-therapy group with higher baseline levels ( ≥ 183 pg/mL · Cr) of urinary 8-isoprostane (p 0.004). Conclusions: EPA may reduce oxidative stress and inhibit the progression of arterial stiffness more efficiently than statin-only therapy in patients with dyslipidemia and CAD. J Atheroscler Thromb, 2011; 18:857-866.

Abstract-The aim of this study was to clarify the differences between the angiotensin II type 1 (AT 1 ) receptor antagonist and the angiotensin-converting enzyme (ACE) inhibitor on smooth muscle and nonmuscle myosin heavy chain isoforms in aortic smooth muscle cells of Wistar-Kyoto rats and spontaneously hypertensive rats. All 4 myosin heavy chain isoforms are heterogeneously expressed in the smooth muscle cells of the aortic tunica media in 20-week-old rats, and the contractile-type myosin heavy chains are highly expressed in smooth muscle cells of the aortic tunica media compared with the synthetic-type myosin heavy chains. Both the AT 1 receptor antagonist and the ACE inhibitor had the same effects on hemodynamics, smooth muscle cell hypertrophy and proliferation, fibrosis, and vascular remodeling in spontaneously hypertensive rats. However, the AT 1 receptor antagonist had a more potent effect on the downregulation of the synthetic-type myosin heavy chains than the ACE inhibitor in spontaneously hypertensive rat aortic tunica media. In contrast, these effects of the AT 1 receptor antagonist and the ACE inhibitor on hemodynamics, morphology, fibrosis, and expression of myosin heavy chain isoforms in smooth muscle cells of the aortic tunica media were not observed in Wistar-Kyoto rats. Thus, within 6 weeks, the AT 1 receptor antagonist might modulate the cellular composition of myosin heavy chain isoforms in smooth muscle cells more efficiently than the ACE inhibitor, without morphological changes in the spontaneously hypertensive rat aorta. (Hypertension. 1999;33:975-980.)Key Words: angiotensin Ⅲ aorta Ⅲ hypertension, arterial Ⅲ muscle, smooth Ⅲ myosin A rterial hypertension is known to result in vascular remodeling. 1 The proliferation of smooth muscle cells (SMC) is also an important component of many vascular diseases. 2,3 Rat vascular SMC contain high levels of both smooth muscle (SM) myosin heavy chain (MHC) and ␣-SM actin and very low levels of nonmuscle myosin heavy chain (NMHC). 4 In addition, they contain at least 4 MHC isoforms: SM-1 (204 kDa), SM-2 (200 kDa), NMHC-A (196 kDa), and NMHC-B (198 kDa). 5 The relative ratios between SM-MHCs and NMHCs are not only determinants of the contractile properties of SM 6 but are also a useful molecular marker for phenotypic changes in SMC. 7 The dedifferentiation process of SMC, known as phenotypic modulation, contributes to the development and/or progression of atherosclerotic diseases. 2,3 SM-MHCs have been shown to be important in the identification of differentiated SMC. 7 On the other hand, it has been demonstrated that NMHCs are most abundantly expressed in embryonic SM and proliferating SMC of arteriosclerotic lesions. 7,8 Medial hypertrophy is associated with changes in the gene expression of vascular SMC, leading to a synthetic phenotype characterized by the accumulation of NMHC. 3 Angiotensin II (Ang II) plays a key role in regulating both the tone and growth of vascular SMC and is directly involved in vascular remodeling. 9 Although Ang II interacts ...

We compared the cardiac effects of the selective angiotensin II type 1 (AT1)-receptor blockade, FK-739, with an angiotensin-converting-enzyme (ACE) inhibitor, enalapril, on left ventricular (LV) distensibility and collagen metabolism in spontaneously hypertensive rats (SHRs). We treated 14-week-old SHRs with FK-739 (30 mg/kg/day) or enalapril (10 mg/kg/day) for 6 weeks. Both FK-739 and enalapril induced a significant decrease in blood pressure (p < 0.001) and regression of LV hypertrophy (p < 0.001) compared with vehicle, with no differences between the treated groups. Furthermore, FK-739 caused a greater decrease in LV collagen content than did enalapril (FK-739-treated group, 3.06 +/- 0.11 mg/g; enalapril-treated group, 3.47 +/- 0.05 mg/g; p = 0.015) with no change in collagen phenotypes. Hearts taken from rats treated with FK-739 also showed greater LV distensibility than those taken from enalapril-treated rats (FK-739-treated group vs. enalapril-treated group at > or = 15 mm Hg, p < 0.001). These results suggest that, compared with ACE inhibition, AT1-receptor blockade may have additional effects on LV distensibility and collagen metabolism in the regression of LV hypertrophy induced by pressure overload.