The Pathogenic Role of Very Low Density Lipoprotein on Atrial Remodeling in the Metabolic Syndrome

Abstract

Atrial fibrillation (AF) is the most common persistent arrhythmia, and can lead to systemic thromboembolism and heart failure. Aging and metabolic syndrome (MetS) are major risks for AF. One of the most important manifestations of MetS is dyslipidemia, but its correlation with AF is ambiguous in clinical observational studies. Although there is a paradoxical relationship between fasting cholesterol and AF incidence, the beneficial benefit from lipid lowering therapy in reduction of AF is significant. Here, we reviewed the health burden from AF and MetS, the association between two disease entities, and the metabolism of triglyceride, which is elevated in MetS. We also reviewed scientific evidence for the mechanistic links between very low density lipoproteins (VLDL), which primarily carry circulatory triglyceride, to atrial cardiomyopathy and development of AF. The effects of VLDL to atria suggesting pathogenic to atrial cardiomyopathy and AF include excess lipid accumulation, direct cytotoxicity, abbreviated action potentials, disturbed calcium regulation, delayed conduction velocities, modulated gap junctions, and sarcomere protein derangements. The electrical remodeling and structural changes in concert promote development of atrial cardiomyopathy in MetS and ultimately lead to vulnerability to AF. As VLDL plays a major role in lipid metabolism after meals (rather than fasting state), further human studies that focus on the effects/correlation of postprandial lipids to atrial remodeling are required to determine whether VLDL-targeted therapy can reduce MetS-related AF. On the basis of our scientific evidence, we propose a pivotal role of VLDL in MetS-related atrial cardiomyopathy and vulnerability to AF.

The role of postprandial very-low-density lipoprotein in the development of atrial remodeling in metabolic syndrome

“…Furthermore, some manifestations of MetS, such as hypertension, diabetes mellitus (DM), and obesity, are independently associated with AF and are attributed to pathogenic mechanisms of atrial remodeling and the development of AF [ 4 – 8 ]. Nevertheless, the findings from clinical studies of the correlation between dyslipidemia and AF are not consistent [ 9 ].…”

Pro-Arrhythmic Signaling of Thyroid Hormones and Its Relevance in Subclinical Hyperthyroidism

“…Risk factors for AF, such as aging, obstructive sleep apnea, diabetes, hypertension, dyslipidemia, obesity, cancer, renal dysfunction, and thyroid diseases, which are all accompanied by deleterious oxidative stress, may act synergistically to cause AF [5,15,[39][40][41][42][43][44], whereby the noncoding microRNAs translate cellular stressors, such as reactive oxygen species, into AF pathogenesis [45]. Emerging evidence suggests a significant role of the altered atrial metabolism, phosphorylation of proteins, inflammatory and autoimmune channelopathies, and presence of autoantibodies to the M2-muscarinic and β 1-adrenergic receptors in the pathogenesis of AF [46][47][48][49][50][51][52][53][54].…”

The Role of Postprandial Very-Low-Density Lipoprotein ­in the Development of Atrial Remodeling in Metabolic Syndrome

“…Furthermore, some manifestations of MetS, such as hypertension, diabetes mellitus (DM), and obesity, are independently associated with AF and are attributed to pathogenic mechanisms of atrial remodeling and the development of AF [4][5][6][7][8]. Nevertheless, the ndings from clinical studies of the correlation between dyslipidemia and AF are not consistent [9].…”