Abbreviations: ARH, autosomal recessive hypercholesterolemia; ASO, antisense oligonucleotide; CAD, coronary artery disease; CVD, cardiovascular disease; EGFA, epidermal growth factor-like repeat homology domain; FH, familial hypercholesterolemia; HDL-C, highdensity lipoprotein cholesterol; HNF1a, hepatocyte nuclear factor 1a; LDL-C, low-density lipoprotein cholesterol; LDLR, LDL receptor; LNA, locked nucleic acid; LOD, logarithm of the odds; monoclonal antibody, MAb; PCSK9, proprotein convertase subtilisin kexin type 9; siRNA, small interfering RNA; SREBP2, sterol-responsive element-binding protein 2.

No abstract

Elevated PCSK9 levels are equally detrimental for patients with HeFH or non-FH: a 100-ng/ml increase in PCSK9 will lead to an increase in LDL-C of 0.20 to 0.25 mmol/l in controls and HeFH alike, irrespective of their LDLR mutation. This explains why patients with non-FH or HeFH respond equally well to monoclonal antibodies targeting PCSK9.

No abstract

Previous studies on rats and human subjects have established that the linoleic acid (LA) requirement is 2 % of the total energy intake (en%), but is obtained in the absence of a-linolenic acid (ALA) and consequently appear to be overestimated. This raises questions since a recent study including ALA has suggested to divide the historical value by four. However, this recent study has remained inconclusive because the animals used were not totally LA-deficient animals. For the first time, the present study was especially designed using physiological and biochemical markers and performed in two steps: (1) to achieve a specific n-6 fatty acid deficiency model using growing male rats fed either a 0 en% from LA/0 en% from ALA (0LA/0ALA), 0LA/0·5ALA or 2LA/0·5ALA diet, born from female rats fed a 0LA/0·5ALA diet; and (2) to refine the required level of LA in the presence of ALA using rats fed either a 0LA/0ALA, 0·5LA/0·5ALA, 1LA/0·5ALA, 1·5LA/0·5ALA diet, born from female rats fed a 0LA/0·5ALA diet. The first step shows that the best LA deficiency model was obtained using rats fed the 0LA/0ALA diet, born from female rats fed the 0LA/0·5ALA diet. The second step demonstrates that in growing rats, LA deficiency was corrected with an intake of 1 -1·5 en% from LA and 0·5 en% from ALA. These data suggest that the requirements in humans should be revisited, considering the presence of ALA to set up the recommendation for LA.