HDL adverse remodelling and dysfunction is a temporal feature that can be reversed. (10th June 2022)

• Record Type: Journal Article
• Authors: Schoch, L; Sutelman, P; Padro, T; Badimon, L; Vilahur, G
• Is Part Of: Cardiovascular research. Volume 118(2022)Supplement 1
• Publication Date: 2022-06-10
• Subjects: Cardiovascular system -- Diseases -- Periodicals; Cardiovascular system -- Periodicals; 616.1
• DOI: 10.1093/cvr/cvac066.165
• Languages: English
• ISSNs: 0008-6363

Abstract

Abstract: Funding Acknowledgements: Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministerio de Ciencia e Innovación (MCIN)/AEI/10.13039/501100011033 and Fondo Europeo de Desarrollo Regional (FFEDER) Background: High-density lipoprotein (HDL) particles have been shown to undergo adverse remodelling and loss of function in the presence of comorbidities. It has been demonstrated that high low-density lipoprotein cholesterol (LDL-C) plasma levels induce compositional changes in HDL particles that render them dysfunctional. It is unknown, however, whether this HDL adverse remodelling is reversible. Purpose: In this preclinical animal study we have investigated whether dyslipidaemia-induced HDL particle remodelling and dysfunction is a permanent adverse change or a temporal trait which can be regulated by dietary intervention. Methods: After 10 days of high-fat diet (HFD) and reaching LDL-C levels of 392.8±94.9 mg/dL, the HDL particles of 15 pigs were characterized. Thereafter, pigs were randomly distributed into two arms. While group 1 was maintained on the same HFD (n=9), group 2 was switched to a normocholesterolemic diet (NCD; n=8) up to day 40. Blood was drawn at days 0 (baseline), 1, 3, 5, and 10 (to characterize HDL dysfunction over the 10-day period of dyslipidaemia induction), and at days 25 and 40 (to assess the HDL particle evolution in the intervention period). We assessed: a) HDL function [cholesterol efflux capacity (CEC) and antioxidant potential]; b) HDL particle number and size by nuclear magnetic resonance; c) oxidative susceptibility of LDL particles; d) HDL protein content of APOA-I, APOM, and APOC-III; and e) biochemical parameters. Results: Up to day 10 there was a time-dependent increase in LDL-C levels that progressively induced the impairment of HDL CEC and antioxidant activity, higher HDL particle numbers, increased formation of conjugated dienes, and lower HDL-APOM content (p<0.01 vs baseline). All these parameters exhibited a plateau at day 10 and remained unchanged up to day 40 in those animals that were kept on HFD. Interestingly, in these animals a strong negative correlation was observed between HDL CEC and HDL-C levels (p<0.0001), with larger HDL particles being detected at day 40 (p<0.05 vs. baseline). On the contrary, all these parameters returned to physiological levels (baseline) in those animals that switched to a NCD (p=ns vs baseline). No changes were detected in APOA-I- and APOC-III- HDL content among animal groups and over time. Conclusion: In the present study we evidence for the first time that dyslipidaemia-induced HDL particle remodelling and dysfunction is not a permanent adverse change. The implementation of a healthy dietary intervention acutely reverses HDL adverse remodelling and dysfunction in a preclinical animal model.