Key result
Darapladib reduces aortic Lp-PLA2 protein but increases mRNA expression in dyslipidemic and T2DM rat models.
Why the study?
Lp-PLA2 activity is suspected to have a significant role in atherosclerosis, but the effect of darapladib therapy on Lp-PLA2 expression in dyslipidemia and T2DM models was unclear.
Does darapladib reduce the expression of Lp-PLA2 in dyslipidemia and Type 2 diabetes mellitus atherosclerosis rat models?
Does darapladib reduce the expression of Lp-PLA2 in dyslipidemia and Type 2 diabetes mellitus atherosclerosis rat models?
In a rat model of dyslipidemia and T2DM, darapladib significantly decreased Lp-PLA2 protein expression but failed to suppress its mRNA expression.
Answers are grounded in this paper and cite their sources.
Darapladib inconsistently modulates Lp-PLA2 in diabetic dyslipidemia rat models; leaves open its net effect on atherosclerosis and clinical translation.
Atherosclerosis is the main cause of mortality and morbidity globally.Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) activity is suspected to have a significant role in atherosclerosis.50 Sprague-Dawley Rats were divided into five groups: normal, dyslipidemia, Type 2 diabetes mellitus (T2DM), dyslipidemia with darapladib administration and T2DM with darapladib administration.These groups were divided into two serial times: 8 and 16 weeks.mRNA Lp-PLA 2 was measured from blood and aortic tissue extraction.Aortic tissue Lp-PLA 2 was measured by immunofluorescence.Lp-PLA 2 expression in aortic tissue was consistently increased in dyslipidemia and T2DM.The expression of Lp-PLA 2 enzymatic was significantly suppressed (p < 0.05) with the administration of darapladib especially in 8 weeks groups in both dyslipidemia and T2DM.The administration of darapladib in dyslipidemia and T2DM didn't significantly suppress the expression of mRNA Lp-PLA 2 in blood and aortic tissue.The failure of genetic expression suppression of Lp-PLA 2 was found in both 8 weeks and 16 weeks groups.The expression of Lp-PLA 2 protein also showed an inclined difference between dyslipidemia and T2DM.These results showed that administration of darapladib significantly decreased Lp-PLA 2 protein but prone to increase the expression of mRNA Lp-PLA 2 in blood and aortic tissue in dyslipidemia and T2DM model.
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A 2018 study studied Dyslipidemia and Type 2 Diabetes Mellitus (n=50). Darapladib vs. Untreated dyslipidemia and T2DM models was evaluated on Lp-PLA2 enzymatic expression in aortic tissue (p=<0.05). Darapladib decreased Lp-PLA2 protein expression in aortic tissue but tended to increase mRNA Lp-PLA2 expression in blood and aortic tissue in dyslipidemia and T2DM rat models.
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