title: PCSK9 and resistin at the crossroads of the atherogenic dyslipidemia.
abstract: The atherogenic dyslipidemia is a pathophysiological lipid triad, composed of high triglycerides and low-density lipoprotein and low high-density lipoprotein. The dyslipidemia is highly prevalent in individuals who are obese, insulin resistant and those with Type 2 diabetes and is the major contributing factor to the high atherosclerotic cardiovascular disease risk in these subjects. The primary initiating event in atherogenic dyslipidemia development is the hepatic overproduction of very-low-density lipoprotein (VLDL). The intracellular and extracellular protein triggers of hepatic VLDL production were not known until the recent identification of the causal roles of PCSK9 and resistin. Both PCSK9 and resistin act in large part by targeting and reducing the hepatic degradation of VLDL apoB through distinctly different mechanisms. In the current review, we discuss both the individual roles and the interaction of these proteins in driving atherogenic dyslipidemia, and thus, atherosclerotic cardiovascular disease progression in humans. We further explore the important therapeutic implications of these findings.
authors.affiliation: Department of Medicine, David Braley Cardiac, Vascular and Stroke Research Institute (DB-CVSRI), McMaster University, Hamilton, Ontario, Canada.
authors.forename: Shirya
authors.initials: S
authors.lastname: Rashid
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
mesh_terms: D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism; D050197:Atherosclerosis / Q000209:etiology* / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000209:etiology / Q000503:physiopathology; D018450:Disease Progression; D050171:Dyslipidemias / Q000150:complications* / Q000453:epidemiology / Q000503:physiopathology; D006801:Humans; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000378:metabolism*; D052243:Resistin / Q000378:metabolism*; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000378:metabolism*
chemical_list: D001055:Apolipoproteins B; D008079:Lipoproteins, VLDL; D052243:Resistin; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases