Spotlight on very-low-density lipoprotein as a driver of cardiometabolic disorders: Implications for disease progression and mechanistic insights

Abstract

Very-low-density lipoprotein (VLDL) is the only lipoprotein containing apolipoprotein B that is secreted from the liver, where VLDL is assembled from apolipoproteins, cholesterol, and triglycerides. The primary function of VLDL is to transport cholesterol and other lipids to organs and cells for utilization. Apart from its role in normal biologic processes, VLDL is also known to contribute to the development of atherosclerotic cardiovascular disease. Large VLDL particles, which are subclassified according to their size by nuclear magnetic resonance spectrometry, are significantly correlated not only with atherosclerosis, but also with insulin resistance and diabetes incidence. VLDL can also be subclassified according to surface electrical charge by using anion-exchange chromatography. The most electronegative VLDL subclass is highly cytotoxic to endothelial cells and may contribute to coronary heart disease. In addition, electronegative VLDL contributes to the development of atrial remodeling, especially in patients with metabolic syndrome, which is an established risk factor for atrial fibrillation. In this review, we focus on the VLDL subclasses that are associated with apolipoprotein alterations and are involved in cardiometabolic disease. The postprandial enhancement of VLDL’s pathogenicity is a critical medical issue, especially in patients with metabolic syndrome. Therefore, the significance of the postprandial modification of VLDL’s chemical and functional properties is extensively discussed.

Nonsevere Burn Induces a Prolonged Systemic Metabolic Phenotype Indicative of a Persistent Inflammatory Response Postinjury

“…As with the lipoproteins, evidence has accumulated of the pro-atherogenic impact that elevated levels of MAG(20:4) has in vivo , mainly through its activation of CB1. − It is hypothesized that MAG(20:4) stimulates monocytes and macrophages to migrate and promote pro-inflammatory cytokine expression, which can result in local vascular inflammation and atherosclerotic plaque formation. , High concentrations of MAG(20:4) have been found in patients with different cardiovascular diseases, such as acute coronary syndrome, obesity-induced cardiac dysfunction, , and chronic heart failure, further indicating a possible avenue for the manifestation of chronic inflammatory and cardiovascular disease risk reported in individuals exposed to burn injury …”

“…86−88 It is hypothesized that MAG(20:4) stimulates monocytes and macrophages to migrate and promote pro-inflammatory cytokine expression, which can result in local vascular inflammation and atherosclerotic plaque formation. 86,88 High concentrations of MAG(20:4) have been found in patients with different cardiovascular diseases, such as acute coronary syndrome, 87 obesity-induced cardiac dysfunction, 89,90 and chronic heart failure, 91 further indicating a possible avenue for the manifestation of chronic inflammatory and cardiovas-cular disease risk reported in individuals exposed to burn injury. 4 In addition to MAGs, TAG species were also reported to be higher in the nonsevere burn group at baseline admission compared with the nonburn controls (Figure 4C).…”

Association of lipid composition and unsaturated fatty acids of VLDL with atrial remodeling in metabolic syndrome

“…Unlike the major effects of statins on the reduction of LDL cholesterol, statins increase the relative abundance of cholesterol in VLDL. Richness of TAG in VLDL particles is found destabilizing HDL from affecting CETP-induced remodeling of TAG-rich HDL, which also affects the lipolysis of VLDL 16 . The withdraw of statin led to a significant reduction of HDL (Table 1 ).…”

“…Lipids were extracted using one-step procedure with methyl tert-butyl ether/methanol (7:2, v/v) was used as a solvent 16 . The procedures and details of the shotgun lipidomics were followed as those presented by Surma et al 29 .…”

“…Independent of LDL, the pathogenic roles of very low-density lipoproteins (VLDL) in the cardiometabolic disorders, including atrial myopathy and AF have been noticed 13 – 16 . In previous studies, the in vivo effects of VLDL extracted from patients with MetS were examined in mice and showed excess lipid accumulation associated with apoptosis in the atria with greater left atrial size and vulnerability to AF 17 .…”