Regular Dietary Intake of Palmitate Causes Vascular and Valvular Calcification in a Rabbit Model.

Nathalie Donis,Philippe Delvenne,Zheshen Jiang,Alain Nchimi,Martin Giera,Céline D'Emal,Niek Blomberg,Cécile Oury,Patrizio Lancellotti,Raluca Dulgheru

doi:10.3389/fcvm.2021.692184

Abstract

Aims: Palmitic acid (PA) and oleic acid (OA) are two main dietary fatty acids. Dietary intake of PA has been associated with cardiovascular disease risk, and the effect of OA remains uncertain. Our study aimed to assess the effect of a short-term intake of lard, as source of PA and OA, on aorta and aortic valve.Methods and Results: Rabbits were fed with two lard-enriched diets, containing either elevated levels of PA or of both PA and OA as compared to chow diet. After 16 weeks of each diet, calcification was observed in the aortic intima and in the aortic valve. The extent of calcification did not differ between the two diets. In contrast, rabbits fed chow diet did not develop any calcification. In blood, PA enrichment resulted in decreased lymphocyte and monocyte counts and increased levels of hemoglobin and haematocrit. Levels of the calcification inhibitor fetuin-A were also diminished, whereas creatinine levels were raised. Of note, none of the diets changed cholesterol levels in LDL or HDL. Comprehensive quantitative lipidomics analysis identified diet-related changes in plasma lipids. Dietary PA enrichment led to a drop of polyunsaturated fatty acids (PUFA), in particular of linoleic acid in cholesteryl esters, triglycerides and diacylglycerols (DAG). Ratios of PA to 18-carbon PUFA in DAG were positively correlated with the extent of aortic valve calcification, and inversely with monocyte counts. PA content in blood correlated with aorta calcification.Conclusions: Regular dietary PA intake induces vascular and valvular calcification independently of traditional risk factors. Our findings raise awareness about PA-rich food consumption and its potential deleterious effect on cardiovascular health.

Highlights

It is well-established that the risk of cardiovascular disease (CVD) is influenced by nutrition habits [1, 2]
It has been found that dietary SFAs do not necessarily increase the risk of CVD, which could be explained by various effects on LDL profiles with distinct atherogenic effects [4], smaller size LDL particles being more likely to penetrate in vessel walls and contributing to atherosclerosis
It contained twice less Oleic acid (18:1) (OA) compared to chow diet

Summary

Introduction

It is well-established that the risk of cardiovascular disease (CVD) is influenced by nutrition habits [1, 2]. It has been long considered that SFAs could increase the risk of CVD. It has been found that dietary SFAs do not necessarily increase the risk of CVD, which could be explained by various effects on LDL profiles (e.g., small dense LDL, large buoyant LDL, very low density lipoproteins, LDL oxidation) with distinct atherogenic effects [4], smaller size LDL particles being more likely to penetrate in vessel walls and contributing to atherosclerosis. Data from the Rotterdam Study revealed that a high risk of coronary artery disease (CAD) was associated with intake of palmitic acid (16:0) (PA), but not of SFA with other chain lengths [7]. In the Multi-Ethnic study of Atherosclerosis, high plasma levels of OA correlated with coronary artery calcification, carotid plaque and aortic valve calcification. To date, there are no experimental studies that investigated whether regular PA or OA intake causes vascular and/or valvular calcification

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Discussion

Conclusion