Peroxisome proliferator-activated receptor α/γ agonist tesaglitazar stabilizes atherosclerotic plaque in diabetic low density lipoprotein receptor knockout mice / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of peroxisome proliferator-activated receptor (PPAR) α/γ agonist on atherosclerotic plaque stabilization in diabetic LDL receptor knockout (LDLr-/-) mice.</p><p><b>METHODS</b>Female 4-week-old LDLr-/- mice fed with high-glucose and high-fat diet for 4 weeks were randomly divided into three groups (n = 15 each): control group (only fed with high-glucose and high-fat diet), diabetic group [induced by high-glucose and high-fat diet combined with a low-dose of streptozotocin (STZ)] without tesaglitazar and with tesaglitazar (20 µg/kg oral treatment). After 6 weeks, the mice were sacrificed, body weight, fasting blood glucose (Glu), total cholesterol (TC), triglyceride (TG) levels were measured. The expression of ICAM-1, VCAM-1, MCP-1 in the brachiocephalic atherosclerotic lesions were determined by Western blot and immunohistochemistry, respectively. Brachiocephalic artery was prepared for morphologic study (HE, oil red O, Sirius red staining) and immunohistochemical analysis (macrophage surface molecule-3, α-smooth muscle actin), respectively.</p><p><b>RESULTS</b>Serum TC [(32.34 ± 3.26) mmol/L vs. (16.17 ± 1.91) mmol/L], TG [(3.57 ± 0.99) mmol/L vs. (2.21 ± 0.11) mmol/L] and Glu [(15.21 ± 4.67) mmol/L vs. (6.89 ± 0.83) mmol/L] levels were significantly higher in diabetic group than in the control group (all P < 0.01). The expression of ICAM-1 (2.31 ± 0.35 vs.1.34 ± 0.21), VCAM-1 (1.65 ± 0.14 vs.0.82 ± 0.26), MCP-1 (2.27 ± 0.16 vs.1.56 ± 0.23) were significantly upregulated in diabetic group compared with control group (all P < 0.01). Brachiocephalic atherosclerotic plaque area [(4.597 ± 1.260)×10(3) µm(2) vs. (0.075 ± 0.030)×10(3) µm(2)], lipid deposition [(47.23 ± 2.64)% vs. (9.67 ± 1.75)%], Mac-3 positive area [(19.15 ± 3.51)% vs. (1.72 ± 0.16)%], α-smooth muscle actin [(5.54 ± 1.17)% vs. (2.13 ± 0.41)%] and collagen content [(4.27 ± 0.74)% vs. (0.43 ± 0.09)%] were all significantly larger/higher in diabetic LDLr-/- mice than in the control group (all P < 0.01). While tesaglitazar treatment significantly reduced serum TC [(30.47 ± 3.18) mmol/L], TG [(3.14 ± 0.71) mmol/L] and Glu [(7.92 ± 1.28) mmol/L] levels (all P < 0.01). Similarly, the expression of ICAM-1 [(1.84 ± 0.22)], VCAM-1 [(1.27 ± 0.11)], MCP-1 [(1.83 ± 0.24)], brachiocephalic atherosclerotic lesion area[(1.283 ± 0.410)×10(3) µm(2)], lipid deposition[(23.52 ± 1.39)%] were also significantly reduced by tesaglitazar (all P < 0.05). Moreover, tesaglitazar increased α-smooth muscle actin [(9.46 ± 1.47)%] and collagen content [(6.32 ± 1.15)%] in diabetic LDLr-/- mice (all P < 0.05). In addition, lipid deposition and Mac-3 positive areas [(10.67 ± 0.88)% vs. (15.83 ± 1.01)%] in the aortic root were also reduced in tesaglitazar treated diabetic LDLr-/- mice (P < 0.01).</p><p><b>CONCLUSIONS</b>Tesaglitazar has anti-inflammatory effects in the diabetic LDLr-/- mice. Tesaglitazar could reduce lipid deposition, increase collagen and α-SMA content in the brachiocephalic atherosclerotic lesions, thus, stabilize atherosclerotic plaque in this model.</p>

The relationship of ankle brachial index to all-cause and cardiovascular disease mortality in Chinese male patients with hypertension / 中华预防医学杂志

<p><b>OBJECTIVE</b>To evaluate the risk factors for peripheral arterial disease (PAD) and the relationship of low ankle brachial index (ABI) to all-cause and cardiovascular disease (CVD) mortality in Chinese male patients with hypertension.</p><p><b>METHODS</b>The data of 1606 male participants with hypertension from the eight hospitals in Beijing and Shanghai were analyzed. ABI was ascertained at baseline by measuring the systolic pressures on bilateral brachial and tibial arteries. ABI < or = 0.9 was used as the diagnostic criteria for PAD identification. The follow-up survey was conducted from November 2005 to January 2006.</p><p><b>RESULTS</b>Of 1606 male participants with hypertension at baseline, 406 (25.3% ) were in low-ABI group and 1200 (74.7%) were in normal-ABI group. Older age, TC, history of diabetes, history of smoking and 2-grade hypertension were associated with low ABI in male patients with hypertension. During the (12.87 +/- 2.94) months follow-up, there were 153 deaths. Of which, 62 were attributable to CVD. Low ABI was associated with adjusted all-cause and CVD mortality risk of 1.728 (1.223-2.441) and 2.388 (1.409-4.046) respectively in Cox regression models. Rate of survival for the low-ABI group was significantly worse than for the normal-ABI group. The risk of all-cause and CVD mortality was increased with the decline of ABI.</p><p><b>CONCLUSION</b>Low ABI is independently associated with the high risks of all-cause and CVD mortality in Chinese male patients with hypertension. The utility of ABI as a tool for predicting mortality in the patients with hypertension should be popularized.</p>