ABSTRACT
Cardiovascular disease (CVD) remains the leading cause of death among adults in the United States. There has been significant advancement in the diagnosis and treatment of atherosclerotic cardiovascular disease (ASCVD) and its underlying risk factors. In certain populations, there remains a significant residual risk despite adequate lowering of low-density lipoprotein cholesterol (LDL-C) and control of traditional risk factors. This has led to an interest in research to identify additional risk factors that contribute to atherosclerotic cardiovascular disease. Elevated lipoprotein (a) [Lp(a)] has been identified as an independent risk factor contributing to an increased risk for CVD. There are also ethnic and racial disparities in Lp(a) inheritance that need to be understood. This paper reviews the current literature on lipoprotein a, proposed mechanisms of actions for cardiovascular disease, recommendations for testing, and the current and emerging therapies for lowering Lp(a).
ABSTRACT
Increased expression of PRKD1 and its gene product protein kinase D1 (PKD1) are linked to oncogenic signaling in pancreatic ductal adenocarcinoma, but a direct functional relationship to oncogenic KRas has not been established so far. We here describe the PRKD1 gene promoter as a target for oncogenic KRas signaling. We demonstrate that KRas-induced activation of the canonical NF-κB pathway is one mechanism of how PRKD1 expression is increased and identify the binding sites for NF-κB in the PRKD1 promoter. Altogether, these results describe a novel mechanism governing PRKD1 gene expression in PDA and provide a functional link between oncogenic KRas, NF-κB and expression of PRKD1.