Arachidonic acid can be metabolized by
cytochrome P450 (CYP450)
enzymes in a tissue- and cell-specific manner to generate vasoactive products such as epoxyeicosatrienoic
acids (EETs-cardioprotective) and
hydroxyeicosatetraenoic acids (HETEs-cardiotoxic). Type II diabetes is a well-recognized risk factor for developing
cardiovascular disease. A mouse model of Type II diabetes (C57BLKS/J-db/db) was used. After sacrifice, livers and hearts were collected, washed, and snap frozen. Total
proteins were extracted. Western blots were performed to assess cardiac CYP2J and hepatic
CYP2C,
CYP4A, and CYP4F
protein expression, respectively. Significant decreases in relative
protein expression of cardiac CYP2J and hepatic
CYP2C were observed in Type II diabetes animals compared to controls (CYP2J: 0.80 ± 0.03 vs. 1.05 ± 0.06, n = 20, p < 0.001); (
CYP2C: 1.56 ± 0.17 vs. 2.21 ± 0.19, n = 19, p < 0.01). In contrast, significant increases in relative
protein expression of both hepatic
CYP4A and CYP4F were noted in Type II diabetes mice compared to controls (
CYP4A: 1.06 ± 0.09 vs. 0.18 ± 0.01, n = 19, p < 0.001); (CYP4F: 2.53 ± 0.22 vs. 1.10 ± 0.07, n = 19, p < 0.001). These alterations induced by Type II diabetes in the endogenous pathway (CYP450) of
arachidonic acid metabolism may increase the risk for
cardiovascular disease by disrupting the fine equilibrium between cardioprotective (CYP2J/
CYP2C-generated) and cardiotoxic (
CYP4A/CYP4F-generated) metabolites of
arachidonic acid.