👤 Julián Verona

Overweight/obesity (OW/OB) is associated with modifications in lipoprotein (Lp)-associated enzymes and proteins, such as cholesteryl ester transfer protein (CETP), Lp-associated phospholipase A To analyze the presence of alterations in Lp-associated enzymes and proteins in children and adolescents with UW and OW/OB and their relation to novel cardiometabolic indexes. Thirty male children and adolescents with UW, 66 with normal weight (NW) and 30 with OW/OB were included. Anthropometric parameters, glucose, Lp profile and the activities of CETP, LpPLA Both UW and OW/OB showed impaired antioxidant PON1 activity. Moreover, TyG, VAI and HLAP were all capable of predicting alterations in crucial modulators of Lp metabolism and vascular inflammation in children and adolescents with varying degrees of alterations in body weight. Show less

Apolipoprotein A-IV amyloidosis is an uncommon form of the disease normally resulting in renal and cardiac dysfunction. ApoA-IV amyloidosis was identified in 16 patients attending the National Amyloidosis Centre and in eight clinical samples received for histology review. Unexpectedly, proteomics identified the presence of ApoA-IV signal sequence residues (p.18-43 to p.20-43) in 16/24 trypsin-digested amyloid deposits but in only 1/266 non-ApoA-IV amyloid samples examined. These additional signal residues were also detected in the cardiac sample from the Swedish patient in which ApoA-IV amyloid was first described, and in plasma from a single cardiac ApoA-IV amyloidosis patient. The most common signal-containing peptide observed in ApoA-IV amyloid, p.20-43, and to a far lesser extent the N-terminal peptide, p.21-43, were fibrillogenic in vitro at physiological pH, generating Congo red-positive fibrils. The addition of a single signal-derived alanine residue to the N-terminus has resulted in markedly increased fibrillogenesis. If this effect translates to the mature circulating protein in vivo, then the presence of signal may result in preferential deposition as amyloid, perhaps acting as seed for the main circulating native form of the protein; it may also influence other ApoA-IV-associated pathologies. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland. Show less

To explore the association between Triglyceride/High-density lipoprotein cholesterol (TG/HDL-C) index and these enzymes and proteins in a pediatric population. Children and adolescents (7-14 y old) were recruited (n = 150) and anthropometric data were registered. Glucose, TG, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), HDL-C plus cholesteryl ester transfer protein (CETP), lipoprotein-associated phospholipase A Twenty-five individuals presented TG/HDL-C ratio ≥ 3.0. These individuals exhibited higher TG [164 (126-186) vs. 65 (48-72) mg/dL; p < 0.01] CETP [250 (232-263) vs. 223 (193-237)% mL/min; p < 0.01] and Lp-PLA Children and adolescents with TG/HDL-C ≥ 3.0 presented a more atherogenic lipid profile and higher CETP and Lp-PLA Show less

Apolipoprotein C-III deficiency provides cardiovascular protection, but apolipoprotein C-III is not known to be associated with human amyloidosis. Here we report a form of amyloidosis characterized by renal insufficiency caused by a new apolipoprotein C-III variant, D25V. Despite their uremic state, the D25V-carriers exhibit low triglyceride (TG) and apolipoprotein C-III levels, and low very-low-density lipoprotein (VLDL)/high high-density lipoprotein (HDL) profile. Amyloid fibrils comprise the D25V-variant only, showing that wild-type apolipoprotein C-III does not contribute to amyloid deposition in vivo. The mutation profoundly impacts helical structure stability of D25V-variant, which is remarkably fibrillogenic under physiological conditions in vitro producing typical amyloid fibrils in its lipid-free form. D25V apolipoprotein C-III is a new human amyloidogenic protein and the first conferring cardioprotection even in the unfavourable context of renal failure, extending the evidence for an important cardiovascular protective role of apolipoprotein C-III deficiency. Thus, fibrate therapy, which reduces hepatic APOC3 transcription, may delay amyloid deposition in affected patients. Show less

We have generated transgenic rabbits that express the entire human apoA-I/C-III/A-IV gene cluster. As in humans, h-apoA-I and h-apoC-III were expressed in liver and intestine, whereas h-apoA-IV mRNA was detected in intestine only. Transgenic rabbits had significantly higher plasma total cholesterol, HDL-cholesterol and total phospholipid concentrations than non-transgenic littermates. In contrast to similar transgenic mice previously generated, which have gross hypertriglyceridemia, triglyceride concentrations were only moderately raised in transgenic rabbits. Plasma and HDL from transgenic rabbits were more effective than those from controls in promoting cholesterol efflux from cultured hepatoma cells. They had lower LCAT, lower CETP and higher PLTP activities than non-transgenic littermates. Cholesterol-feeding produced major increases in plasma lipids. The qualitative response to the diet was not modified by cluster expression. Human apoA-I concentration was halved by cholesterol-feeding, whereas h-apoC-III and h-apoA-IV concentrations were not significantly altered. Cholesterol efflux from hepatoma cells to plasma and HDL was not altered by the diet. Since lipoprotein metabolism of rabbits closely resembles that of humans, human apoA-I/C-III/A-IV transgenic rabbits may provide a reliable model for studies of the transcriptional regulation of the cluster, and for evaluating the effects of different agents on the expression of the three genes. Show less