Clinical and experimental pharmacology & physiology
-
Clin. Exp. Pharmacol. Physiol. · Jan 2011
Artemisinin inhibits extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase-9 expression via a protein kinase Cδ/p38/extracellular signal-regulated kinase pathway in phorbol myristate acetate-induced THP-1 macrophages.
1. Overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinases (MMPs) by monocytes/macrophages has been proposed to play a significant role in atherosclerotic plaque progression and rupture. The aim of the present study was to explore whether artemisinin, a natural extract from Artemisia annua, could decrease EMMPRIN and MMP-9 expression in phorbol myristate acetate (PMA)-induced macrophages by regulating the protein kinase (PK) Cδ/c-Jun N-terminal kinase (JNK)/p38/extracellular signal-regulated kinase (ERK) pathway. 2. ⋯ In addition, artemisinin (20-80 μg/mL) strongly blocked PKCδ/JNK/p38/ERK MAPK phosphorylation. The PKCδ inhibitor rottlerin (1-10 μmol/L) also significantly inhibited JNK/p38/ERK phosphorylation and decreased EMMPRIN and MMP-9 mRNA and protein expression. 4. The results of the present study suggest that artemisinin inhibits EMMPRIN and MMP-9 expression and activity by suppressing the PKCδ/ERK/p38 cascade in PMA-induced macrophages.
-
Clin. Exp. Pharmacol. Physiol. · Jan 2011
Comparative StudyCytochrome P450 2J3/epoxyeicosatrienoic acids mediate the cardioprotection induced by ischaemic post-conditioning, but not preconditioning, in the rat.
1. Cytochrome P450 (CYP) epoxygenases and their arachidonic acid metabolites play a protective role against ischaemia-reperfusion injury. In the present study, we investigated whether endogenous CYP2J3/epoxyeicosatrienoic acid (EET) mediates the cardioprotective effects of ischaemic preconditioning (IPC) and ischaemic post-conditioning (IPost). 2. ⋯ Interestingly, IPost, but not IPC, significantly increased CYP2J3 mRNA (1.75 ± 0.22 vs 1.0; P < 0.05) and protein (1.62 ± 0.22 vs 1.0; P < 0.05), as well as 11,12-EET synthesis compared to I/R (6.2 ± 0.2 vs 2.9 ± 0.2 ng/mg wet weight, respectively; P < 0.01). Administration of MS-PPOH before ischaemia significantly decreased 11,12-EET synthesis in both IPC and IPost compared with I/R rats (2.1 ± 0.2, 3.2 ± 0.3 and 2.9 ± 0.2 ng/mg wet weight, respectively; P < 0.01), but decreased the cardioprotective effects, as evidenced by cardiac function and myocardial infarct size, of IPost only. 4. These data indicate that endogenous activation of CYP2J3/EET may be an essential trigger leading to the protective effects of IPost, but not IPC, in the rat heart.
-
Clin. Exp. Pharmacol. Physiol. · Jan 2011
Clinical TrialAssociation between brachial-ankle pulse wave velocity and endothelium-dependent and -independent coronary vasomotor function.
1. Coronary endothelial function and brachial-ankle pulse wave velocity (baPWV) are independent predictors of cardiovascular events. Thus, in the present study we examined the relationship between baPWV and endothelium-dependent and -independent coronary vasodilatory functions. 2. ⋯ Multivariate analysis revealed diabetes to be independently and significantly associated with baPWV, BK-induced Δ%CBF and Δ%CoD and Pa-induced Δ%CBF. 5. In conclusion, the results of the present study suggest that increased baPWV is associated with endothelium-dependent and -independent coronary vasodilatory dysfunction. Non-invasive and straightforward baPWV measurement may be useful for the assessment of coronary risk factors, particularly in diabetic patients.