Effects of a PPAR- (Peroxisome γ Proliferator-Activated Receptor-gamma) Activator on Flow-Mediated Brachial Artery Dilation and Circulating Level of microRNA-21 in Hypertensive Type 2 Diabetic Patientss
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background: Endothelial dysfunction has been documented in patients with type 2 diabetes especially when combined with hypertension. We prospectively investigated the effects of pioglitazone in improving endothelial function in hypertensive type 2 diabetic patients during the 6-month follow-up. Methods: Hypertensive type 2 diabetic patients were randomly assigned to pioglitazone (n = 25) or placebo (n = 25). Primary endpoint was to compare changes in brachial artery flow-mediated dilation (baFMD) between the 2 groups during the 6-month follow-up. Secondary endpoints were to compare changes in the circulating levels of microRNA-17, -21, 92a, -126, and -145 which have been known as indicators of endothelial cell migration and atherosclerosis progression during the 6-month follow-up. Inflammatory markers such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), high-sensitive C-reactive protein, adiponectin, soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were compared during the follow-up. Results: The prevalences of risk factors such as hyperlipidemia, smoking, stroke, and family history of coronary artery disease did not show significant differences between the 2 groups. Increases in baFMD (0.33 ± 0.34 mm vs. 0.02 ± 0.25 mm, p ＜0.05, respectively) and in the level of circulating microRNA-21 (0.23 ± 0.05 vs. -0.06 ± 0.04, p ＜0.05, respectively) were significantly greater in the pioglitazone group when compared to the placebo group during the 6-month follow-up. No significant differences in the prevalences of new onset heart failure, fracture, and bladder cancer were noted during the follow-up between the 2 groups. Decreases in the levels of inflammatory marker such as IL-6 (-2.54 ± 2.32 pg/mL vs. -1.34 ± 2.12 pg/mL, p ＜ 0.05, respectively), TNF-α (-1.54 ± 1.51 pg/mL vs. 0.14 ± 1.12 pg/mL, p ＜ 0.05, respectively), sICAM-1 (-39 ± 52 ng/mL vs. 6 ± 72 ng/mL, p ＜0.05, respectively), and sVCAM-1 (-154 ± 198 ng/mL vs. -11 ± 356 ng/mL, p ＜ 0.05, respectively) were significantly greater in the pioglitazone group compared to the placebo group during the follow-up. Conclusions: In hypertensive type 2 diabetic patients, pioglitazone may increase baFMD and circulatory microRNA-21 and decrease inflammatory cytokines including IL-6, TNF-α, sICAM-1, and sVCAM-1.
Abstract
Background: Endothelial dysfunction has been documented in patients with type 2 diabetes especially when combined with hypertension. We prospectively investigated the effects of pioglitazone in improving endothelial function in hypertensive type 2 diabetic patients during the 6-month follow-up. Methods: Hypertensive type 2 diabetic patients were randomly assigned to pioglitazone (n = 25) or placebo (n = 25). Primary endpoint was to compare changes in brachial artery flow-mediated dilation (baFMD) between the 2 groups during the 6-month follow-up. Secondary endpoints were to compare changes in the circulating levels of microRNA-17, -21, 92a, -126, and -145 which have been known as indicators of endothelial cell migration and atherosclerosis progression during the 6-month follow-up. Inflammatory markers such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), high-sensitive C-reactive protein, adiponectin, soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were compared during the follow-up. Results: The prevalences of risk factors such as hyperlipidemia, smoking, stroke, and family history of coronary artery disease did not show significant differences between the 2 groups. Increases in baFMD (0.33 ± 0.34 mm vs. 0.02 ± 0.25 mm, p ＜0.05, respectively) and in the level of circulating microRNA-21 (0.23 ± 0.05 vs. -0.06 ± 0.04, p ＜0.05, respectively) were significantly greater in the pioglitazone group when compared to the placebo group during the 6-month follow-up. No significant differences in the prevalences of new onset heart failure, fracture, and bladder cancer were noted during the follow-up between the 2 groups. Decreases in the levels of inflammatory marker such as IL-6 (-2.54 ± 2.32 pg/mL vs. -1.34 ± 2.12 pg/mL, p ＜ 0.05, respectively), TNF-α (-1.54 ± 1.51 pg/mL vs. 0.14 ± 1.12 pg/mL, p ＜ 0.05, respectively), sICAM-1 (-39 ± 52 ng/mL vs. 6 ± 72 ng/mL, p ＜0.05, respectively), and sVCAM-1 (-154 ± 198 ng/mL vs. -11 ± 356 ng/mL, p ＜ 0.05, respectively) were significantly greater in the pioglitazone group compared to the placebo group during the follow-up. Conclusions: In hypertensive type 2 diabetic patients, pioglitazone may increase baFMD and circulatory microRNA-21 and decrease inflammatory cytokines including IL-6, TNF-α, sICAM-1, and sVCAM-1.
참고문헌 (27)
- Moody WE, "Endothelial dysfunction and cardiovascular disease in early-stage chronic kidney disease: cause or association?", Atherosclerosis, 223, pp.86~94 (2012)
- Weiss TW, "Components of the interleukin-6 transsignalling system are associated with the metabolic syndrome, endothelial dysfunction and arterial stiffness", Metabolism, 62, pp.1008~1013 (2013)
- Hong SJ, "Comparison of efficacy and tolerability of amlodipine orotate versus amlodipine besylate in adult patients with mild to moderate hypertension : a multicenter, randomized, double-blind, placebo-controlled, parallel-group, 8-week follow-up, noninferiority trial", Clin Ther, 28, pp.537~551 (2006)
- Bakris G, "Comparison of benazepril plus amlodipine or hydrochlorothiazide in high-risk patients with hypertension and coronary artery disease", Am J Cardiol, 112, pp.255~259 (2013)
- Lee DC, "Changes in fitness and fatness on the development of cardiovascular disease risk factors hypertension, metabolic syndrome, and hypercholesterolemia", J Am Coll Cardiol, 59, pp.665~672 (2012)
- Hong SJ, "Telmisartan reduces neointima volume and pulse wave velocity 8 months after zotarolimus-eluting stent implantation in hypertensive type 2 diabetic patients", Heart, 97, pp.1425~1432 (2011)
- Hong SJ, "Cellular and molecular changes associated with inhibitory effect of pioglitazone on neointimal growth in patients with type 2 diabetes after zotarolimus-eluting stent implantation", Arterioscler Thromb Vasc Biol, 30, pp.2655~2665 (2010)
- 진동규, "당뇨가 있는 고혈압 환자에서 목표 혈압을 얼마까지 할 것인가?", 대한고혈압학회지, 17(1), pp.10~16 (2011), 대한고혈압학회
- Mizoguchi M, "Pioglitazone attenuates atherosclerotic plaque inflammation in patients with impaired glucose tolerance or diabetes a prospective, randomized, comparator-controlled study using serial FDG PET", CT imaging study of carotid artery and ascending aorta, 2011, pp.4, 1110~1118
- Hsiao FY, "Risk of bladder cancer in diabetic patients treated with rosiglitazone or pioglitazone : a nested case-control study", Drug Saf, 36, pp.643~649 (2013)
- Ferwana M, "Pioglitazone and risk of bladder cancer : a meta-analysis of controlled studies", Diabet Med, 30, pp.1026~1032 (2013)
- Aubert RE, "Rosiglitazone and pioglitazone increase fracture risk in women and men with type 2 diabetes", Diabetes Obes Metab, 12, pp.716~721 (2010)
- Loke YK, "Long-term use of thiazolidinediones and fractures in type 2 diabetes : a meta-analysis", CMAJ, 180, pp.32~39 (2009)
- Fichtlscherer S, "Circulating microRNAs: biomarkers or mediators of cardiovascular diseases?", Arterioscler Thromb Vasc Biol, 31, pp.2383~2390 (2011)
- Meigs JB, "Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus", JAMA, 291, pp.1978~1986 (2004)
- Libby P, "Inflammation in diabetes mellitus: role of peroxisome proliferator-activated receptor-alpha and peroxisome proliferator-activated receptor-gamma agonists", Am J Cardiol, 99, pp.27B~40B (2007)
- Hallberg C, "Effect of fatty acid on HDL-mediated efflux of cholesterol in THP-1 uman macrophages and human monocytes-derived macrophages", Chem Phys Lipids, 136, pp.132~133 (2005)
- Stephen Y. Chan, MD, "MicroRNA in the Diseased Pulmonary Vasculature: Implications for the Basic Scientist and Clinician", 대한고혈압학회지, 19(1), pp.1~16 (2013), 대한고혈압학회
- Jazbutyte V, "MicroRNA-21 : from cancer to cardiovascular disease", Current Drug Targets, 11, pp.926~935 (2010)
- Cheng Y, "MicroRNA-21 in cardiovascular disease", J Cardiovasc Transl Res, 3, pp.251~255 (2010)
- Kaluza D, "Histone deacetylase 9 promotes angiogenesis by targeting the antiangiogenic microRNA-17-92 cluster in endothelial cells", Arterioscler Thromb Vasc Biol, 33, pp.533~543 (2013)
- Wu W, "Flow-Dependent Regulation of Kruppel-Like Factor 2 Is Mediated by MicroRNA-92a", Circulation, 124, pp.633~641 (2011)
- Wei Y, "MicroRNA-126, -145, and -155: a therapeutic triad in atherosclerosis?", Arterioscler Thromb Vasc Biol, 33, pp.449~454 (2013)
- Maachi M, "Systemic low-grade inflammation is related to both circulating and adipose tissue TNF alpha, leptin and IL-6 levels in obese women", Int J Obesity, 28, pp.993~997 (2004)
- 유성혜, "The Effects of Pioglitazone in Reducing Atherosclerosis Progression and Neointima Volume in Type 2 Diabetic Patients: Prospective Randomized Study With Volumetric Intravascular Ultrasonography Analysis", Korean Circulation Journal, 40(12), pp.625~631 (2010), 대한심장학회
- Hong SJ, "Decrease in plasma adiponectin concentrations in patients with variant angina and acute coronary syndrome", Am J Cardiol, 95, pp.61A~62A (2005)
- Cybulsky MI, "A major role for VCAM-1, but not ICAM-1, in early atherosclerosis", J Clin Invest, 107, pp.1255~1262 (2001)