Atherosclerosis and Coenzyme Q10

Abstract

Atherosclerosis is the most common cause of cardiac deaths worldwide. Classically, atherosclerosis has been explained as a simple arterial lipid deposition with concomitant loss of vascular elasticity. Eventually, this condition can lead to consequent blood flow reduction through the affected vessel. However, numerous studies have demonstrated that more factors than lipid accumulation are involved in arterial damage at the cellular level, such as inflammation, autophagy impairment, mitochondrial dysfunction, and/or free-radical overproduction. In order to consider the correction of all of these pathological changes, new approaches in atherosclerosis treatment are necessary. Ubiquinone or coenzyme Q₁₀ is a multifunctional molecule that could theoretically revert most of the cellular alterations found in atherosclerosis, such as cholesterol biosynthesis dysregulation, impaired autophagy flux and mitochondrial dysfunction thanks to its redox and signaling properties. In this review, we will show the latest advances in the knowledge of the relationships between coenzyme Q₁₀ and atherosclerosis. In addition, as atherosclerosis phenotype is closely related to aging, it is reasonable to believe that coenzyme Q₁₀ supplementation could be beneficial for both conditions.

Keywords: aging; atherosclerosis; coenzyme Q10; ubiquinone.

Figure 1

Coenzyme Q₁₀ (CoQ) effects on atherosclerosis. CoQ is a lipophilic molecule composed by a benzoquinone ring conjugated to an isoprenoid chain of ten units in humans, which are the basis for its redox and lipophilic properties respectively. This molecule has a pleiotropic effect at several levels: Membrane antioxidant, cell signaling, gene expression and mitochondria function.

Figure 2

Working model of FH physiopathology and the effects of CoQ. First, LDL-C uptake is impaired, due to LDL-R mutations, provoking high levels of LDL-C in the blood. At the cellular level, poor extracellular cholesterol uptake will also result in dysregulated mevalonate pathway, which leads to cholesterol accumulation and secondary CoQ deficiency. Intracellular cholesterol accumulation is associated with SREBP-2 activation and increased HMGCR and cholesterogenic enzymes expression levels. As a consequence, CoQ biosynthesis, the other main sub-branch of the mevalonate pathway, is defective inducing mitochondrial dysfunction, oxidative stress, impaired autophagy flux and inflammasome activation. Interestingly, all these alterations are also involved in cell senescence. CoQ treatment can correct both altered mevalonate pathway and mitochondrial dysfunction in FH fibroblasts. CoQ causes a significant increased expression of LDL-R and ABCA1 accompanied by downregulation of PCSK9, as well as AMPK and PPAR-α activation. In addition, CoQ restores INSIG1 and INSIG2 expression levels (involved in intracellular cholesterol sensing) and allows the normal feedback inhibition of SREBP-2 activation when cholesterol levels are high. The beneficial effects of CoQ on mitochondrial function can also be attributed to CoQ biosynthetic pathway up-regulation. ABCA1, ATP-binding cassette transports A1; AMPK, AMP-activated protein kinase; CoQ, Coenzyme Q₁₀; HMGCR, 3-Hydroxy-3-Methyl-Glutaryl-Coenzyme A Reductase; FPP, Farnesyl Pyrophosphate; LDL-C, Low Density Lipoprotein Cholesterol; LDL-R, Low Density Lipoprotein Receptor; PCSK9, Proprotein Convertase Subtilisin/Kexin type 9; PPAR-α, Peroxisome proliferator-activated receptors α; SREBP2, Sterol regulatory element-binding proteins.