Vinegars but not acetic acid are effective in reducing plasma cholesterol in hamsters fed a high-cholesterol diet

Vinegars reduce plasma cholesterol in hamsters given a high cholesterol diet.

My road to Damascus: how I converted to the prohormone theory and the proprotein convertases

My desire as a young endocrinologist to improve my clinical skills through a better knowledge of hormone chemistry led me to serendipitous discoveries and unexpected horizons. The first discovery, published in 1967, revealed that peptide hormones are derived from endoproteolytic cleavages of larger precursor polypeptides. It was the foundation of the prohormone theory. Initially thought to apply to a few hormones, the theory rapidly extended to many proteins, including neuropeptides, neurotrophins, growth and transcription factors, receptors, extracellular matrix proteins, bacterial toxins, and viral glycoproteins. Its endoproteolytic activation mechanism has become a fundamental cellular process, affecting many biological functions. It implied the existence of specific endoproteolytic enzymes. These proprotein convertases were discovered in 1990. They have been shown to play a wide range of important roles in health and disease. They have opened up novel therapeutic avenues. Inactivation of PCSK9 to reduce plasma cholesterol is currently the most promising. To make this good thing even better, I recently discovered in a French Canadian family a potent PCSK9 (Gln152His) mutation that significantly lowers plasma cholesterol and should confer cardiovascular longevity. The discovery helped me to complete the loop: “From the bedside to the bench and back to the bedside.”

Hypocholesterolaemic effects of plant sterol analogues are independent of ABCG5 and ABCG8 transporter expressions in hamsters

The hypolipidaemic effects of plant sterols are well established. However, mechanisms by which plant sterols lower plasma cholesterol levels, particularly at the molecular level, have not been clearly elucidated. The objective of the present study was to determine whether different plant sterol analogues reduce plasma cholesterol levels by up regulating the sterol transporters ABCG5 and ABCG8 in the liver and/or small intestine. Male Golden Syrian hamsters were divided into eight groups. Groups 1 and 2 were fed a maize starch–casein–sucrose-based diet that did not contain cholesterol (control; Con) or the Con diet with the addition of 0·25 % cholesterol (Ch-Con). Groups 3–8 were fed the Ch-Con diet supplemented with 1 % plant sterols, 1 % plant stanols, 1 % of a plant sterol and stanol mixture (50:50), 1·76 % plant sterol–fish oil esters, or 0·71 or 1·43 % stanol–ascorbic acid esters, respectively. After 5 weeks, the Ch-Con diet up regulated the ABCG5 mRNA expression and tended (P = 0·083) to increase ABCG8 mRNA expression in the liver, but did not affect both genes’ expression in the small intestine compared with the Con diet. Hamsters fed 0·7 % stanol esters showed lower plasma cholesterol levels (P < 0·001) and also lower liver ABCG5 mRNA expression (P < 0·05) compared with the Ch-Con diet. Plant stanols, stanol esters, and sterol esters did not affect the ABCG5 or ABCG8 mRNA expressions in the liver and intestine although they reduced plasma cholesterol levels. These results suggest that plant sterols and their derivatives reduce plasma cholesterol levels independently from the mRNA expression of ABCG5 and ABCG8 transporters.