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Valsartan decreases platelet activity and arterial thrombotic events in elderly patients with hypertension.

Wu F, Wang HY, Cai F, Wang LJ, Zhang FR, Chen XN, Yang Q, Jiang MH, Wang XF, Shen WF - Chin. Med. J. (2015)

Bottom Line: PAR was lower after treatment with valsartan (11.49 ± 0.69% vs. 18.71 ± 2.47%, P < 0.001), associated with more reduced plasma levels of COX-2 (76.94 ± 7.07 U/L vs. 116.4 ± 15.89 U/L, P < 0.001) and TXB 2 (1667 ± 56.50 pg/ml vs. 2207 ± 180.20 pg/ml) (all P < 0.001).During follow-up (median, 18 months), there was a significantly lower thrombotic event rate in patients treated with valsartan (14.3% vs. 32.8%, P = 0.002).Relative expression of COX-2 and secretion of TXB 2 with concordant phosphorylation of p38MAPK and NF-kB were increased in HAECs when stimulated by Ang II (100 nmol/L) but were significantly decreased by valsartan pretreatment (100 nmol/L).

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Ruijin Hospital, Jiao Tong University School of Medicine, Shanghai 200025, China.

ABSTRACT

Background: Angiotensin type 1 receptor (AT 1 R) antagonists are extensively used for blood pressure control in elderly patients with hypertension. This study aimed to investigate the inhibitory effects of AT 1 R antagonist valsartan on platelet aggregation and the occurrence of cardio-cerebral thrombotic events in elderly patients with hypertension.

Methods: Two-hundred and ten patients with hypertension and aged > 60 years were randomized to valsartan (n = 140) or amlodipine (n = 70) on admission. The primary endpoint was platelet aggregation rate (PAR) induced by arachidonic acid at discharge, and the secondary endpoint was the rate of thrombotic events including brain infarction and myocardial infarction during follow-up. Human aortic endothelial cells (HAECs) were stimulated by angiotensin II (Ang II, 100 nmol/L) with or without pretreatment of valsartan (100 nmol/L), and relative expression of cyclooxygenase-2 (COX-2) and thromboxane B 2 (TXB 2 ) and both p38 mitogen-activated protein kinase (p38MAPK) and nuclear factor-kB (NF-kB) activities were assessed. Statistical analyses were performed by GraphPad Prism 5.0 software (GraphPad Software, Inc., California, USA).

Results: PAR was lower after treatment with valsartan (11.49 ± 0.69% vs. 18.71 ± 2.47%, P < 0.001), associated with more reduced plasma levels of COX-2 (76.94 ± 7.07 U/L vs. 116.4 ± 15.89 U/L, P < 0.001) and TXB 2 (1667 ± 56.50 pg/ml vs. 2207 ± 180.20 pg/ml) (all P < 0.001). Plasma COX-2 and TXB 2 levels correlated significantly with PAR in overall patients (r = 0.109, P < 0.001). During follow-up (median, 18 months), there was a significantly lower thrombotic event rate in patients treated with valsartan (14.3% vs. 32.8%, P = 0.002). Relative expression of COX-2 and secretion of TXB 2 with concordant phosphorylation of p38MAPK and NF-kB were increased in HAECs when stimulated by Ang II (100 nmol/L) but were significantly decreased by valsartan pretreatment (100 nmol/L).

Conclusions: AT 1 R antagonist valsartan decreases platelet activity by attenuating COX-2/TXA 2 expression through p38MAPK and NF-kB pathways and reduces the occurrence of cardio-cerebral thrombotic events in elderly patients with hypertension.

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Valsartan inhibited angiotensin II (Ang II) induced cyclooxygenase-2 (COX-2) and phosphorylation of p38 mitogen-activated protein kinase (p38MAPK)/nuclear factor-kB in human aortic endothelial cells. (a) Valsartan's effect on COX-2 mRNA expression induced by Ang II (100 nmol/L); *P < 0.01. (b) Valsartan's (100 nmol/L) effect on COX-2 protein expression induced by Ang II (100 nmol/L); (c) Valsartan's (100 nmol/L) effect on p38 mitogen-activated protein kinase (p38MAPK), phosphorylation of p38MAPK, phosphorylation of nuclear factor-kB (NF-kB), NF-kB expression induced by Ang II (100 nmol/L). C means control group, Ang means Ang II group, Val + Ang means Valsartan + Ang II group. Data represent the mean ± standard deviation (n = 3).
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Figure 4: Valsartan inhibited angiotensin II (Ang II) induced cyclooxygenase-2 (COX-2) and phosphorylation of p38 mitogen-activated protein kinase (p38MAPK)/nuclear factor-kB in human aortic endothelial cells. (a) Valsartan's effect on COX-2 mRNA expression induced by Ang II (100 nmol/L); *P < 0.01. (b) Valsartan's (100 nmol/L) effect on COX-2 protein expression induced by Ang II (100 nmol/L); (c) Valsartan's (100 nmol/L) effect on p38 mitogen-activated protein kinase (p38MAPK), phosphorylation of p38MAPK, phosphorylation of nuclear factor-kB (NF-kB), NF-kB expression induced by Ang II (100 nmol/L). C means control group, Ang means Ang II group, Val + Ang means Valsartan + Ang II group. Data represent the mean ± standard deviation (n = 3).

Mentions: After pretreatment with valsartan (100 nmol/L), HAECs were stimulated with Ang II (100 nmol/L) for 10 min to detect the p-p38MAPK and p-NF-kB, 1 h to detect COX-2 mRNA and 3 h to detect COX-2 protein. Valsartan (100 nmol/L) significantly inhibited Ang II-induced COX-2 mRNA and protein expression (P < 0.001) [Figure 4a and 4b], with parallel decrease in p-p38MAPK and p-NF-kB [Figure 4c].


Valsartan decreases platelet activity and arterial thrombotic events in elderly patients with hypertension.

Wu F, Wang HY, Cai F, Wang LJ, Zhang FR, Chen XN, Yang Q, Jiang MH, Wang XF, Shen WF - Chin. Med. J. (2015)

Valsartan inhibited angiotensin II (Ang II) induced cyclooxygenase-2 (COX-2) and phosphorylation of p38 mitogen-activated protein kinase (p38MAPK)/nuclear factor-kB in human aortic endothelial cells. (a) Valsartan's effect on COX-2 mRNA expression induced by Ang II (100 nmol/L); *P < 0.01. (b) Valsartan's (100 nmol/L) effect on COX-2 protein expression induced by Ang II (100 nmol/L); (c) Valsartan's (100 nmol/L) effect on p38 mitogen-activated protein kinase (p38MAPK), phosphorylation of p38MAPK, phosphorylation of nuclear factor-kB (NF-kB), NF-kB expression induced by Ang II (100 nmol/L). C means control group, Ang means Ang II group, Val + Ang means Valsartan + Ang II group. Data represent the mean ± standard deviation (n = 3).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837831&req=5

Figure 4: Valsartan inhibited angiotensin II (Ang II) induced cyclooxygenase-2 (COX-2) and phosphorylation of p38 mitogen-activated protein kinase (p38MAPK)/nuclear factor-kB in human aortic endothelial cells. (a) Valsartan's effect on COX-2 mRNA expression induced by Ang II (100 nmol/L); *P < 0.01. (b) Valsartan's (100 nmol/L) effect on COX-2 protein expression induced by Ang II (100 nmol/L); (c) Valsartan's (100 nmol/L) effect on p38 mitogen-activated protein kinase (p38MAPK), phosphorylation of p38MAPK, phosphorylation of nuclear factor-kB (NF-kB), NF-kB expression induced by Ang II (100 nmol/L). C means control group, Ang means Ang II group, Val + Ang means Valsartan + Ang II group. Data represent the mean ± standard deviation (n = 3).
Mentions: After pretreatment with valsartan (100 nmol/L), HAECs were stimulated with Ang II (100 nmol/L) for 10 min to detect the p-p38MAPK and p-NF-kB, 1 h to detect COX-2 mRNA and 3 h to detect COX-2 protein. Valsartan (100 nmol/L) significantly inhibited Ang II-induced COX-2 mRNA and protein expression (P < 0.001) [Figure 4a and 4b], with parallel decrease in p-p38MAPK and p-NF-kB [Figure 4c].

Bottom Line: PAR was lower after treatment with valsartan (11.49 ± 0.69% vs. 18.71 ± 2.47%, P < 0.001), associated with more reduced plasma levels of COX-2 (76.94 ± 7.07 U/L vs. 116.4 ± 15.89 U/L, P < 0.001) and TXB 2 (1667 ± 56.50 pg/ml vs. 2207 ± 180.20 pg/ml) (all P < 0.001).During follow-up (median, 18 months), there was a significantly lower thrombotic event rate in patients treated with valsartan (14.3% vs. 32.8%, P = 0.002).Relative expression of COX-2 and secretion of TXB 2 with concordant phosphorylation of p38MAPK and NF-kB were increased in HAECs when stimulated by Ang II (100 nmol/L) but were significantly decreased by valsartan pretreatment (100 nmol/L).

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Ruijin Hospital, Jiao Tong University School of Medicine, Shanghai 200025, China.

ABSTRACT

Background: Angiotensin type 1 receptor (AT 1 R) antagonists are extensively used for blood pressure control in elderly patients with hypertension. This study aimed to investigate the inhibitory effects of AT 1 R antagonist valsartan on platelet aggregation and the occurrence of cardio-cerebral thrombotic events in elderly patients with hypertension.

Methods: Two-hundred and ten patients with hypertension and aged > 60 years were randomized to valsartan (n = 140) or amlodipine (n = 70) on admission. The primary endpoint was platelet aggregation rate (PAR) induced by arachidonic acid at discharge, and the secondary endpoint was the rate of thrombotic events including brain infarction and myocardial infarction during follow-up. Human aortic endothelial cells (HAECs) were stimulated by angiotensin II (Ang II, 100 nmol/L) with or without pretreatment of valsartan (100 nmol/L), and relative expression of cyclooxygenase-2 (COX-2) and thromboxane B 2 (TXB 2 ) and both p38 mitogen-activated protein kinase (p38MAPK) and nuclear factor-kB (NF-kB) activities were assessed. Statistical analyses were performed by GraphPad Prism 5.0 software (GraphPad Software, Inc., California, USA).

Results: PAR was lower after treatment with valsartan (11.49 ± 0.69% vs. 18.71 ± 2.47%, P < 0.001), associated with more reduced plasma levels of COX-2 (76.94 ± 7.07 U/L vs. 116.4 ± 15.89 U/L, P < 0.001) and TXB 2 (1667 ± 56.50 pg/ml vs. 2207 ± 180.20 pg/ml) (all P < 0.001). Plasma COX-2 and TXB 2 levels correlated significantly with PAR in overall patients (r = 0.109, P < 0.001). During follow-up (median, 18 months), there was a significantly lower thrombotic event rate in patients treated with valsartan (14.3% vs. 32.8%, P = 0.002). Relative expression of COX-2 and secretion of TXB 2 with concordant phosphorylation of p38MAPK and NF-kB were increased in HAECs when stimulated by Ang II (100 nmol/L) but were significantly decreased by valsartan pretreatment (100 nmol/L).

Conclusions: AT 1 R antagonist valsartan decreases platelet activity by attenuating COX-2/TXA 2 expression through p38MAPK and NF-kB pathways and reduces the occurrence of cardio-cerebral thrombotic events in elderly patients with hypertension.

Show MeSH
Related in: MedlinePlus