Autoantibodies to apolipoprotein A-1 as a biomarker of cardiovascular autoimmunity

Figure 1 Deaths by cause in Europe for the latest available year, and by gender. Adapted from European Heart Network (http://www.ehnheart.org). CVD: cardiovascular disease.

Figure 2 Annual evolution of publications on cardiac biomarkers since 2000. This graphic represents the number of publications per year indexed and retrieved in Pubmed between 2000 and 2012 when the key words “cardiovascular biomarkers” are entered. Entry date: 22^nd of January 2014.

Figure 3 Autoantibodies against apolipoprotein A-1 IgG elicit a pro-inflammatory response through Toll-like receptor 2/CD14 complex on human macrophages. Autoantibodies against apolipoprotein A-1 (anti-apoA-1) IgG specifically bind to Toll-like receptor (TLR)2 due to conformational homology between apoA-1 and TLR2. In the presence of CD14, the binding of anti-apoA-1 IgG to TLR2 induces a nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-dependent production of pro-inflammatory cytokines. MMP-9: Matrix-metalloproteinases; IL-8: Interleukin-8.

Figure 4 Current understanding of the mechanism by which autoantibodies against apolipoprotein A-1 IgG elicit chronotropic responses in nenonatal rat cardiomyocytes. Stimulation of the mineralocorticoid receptor (MR), either by aldosterone or oxidized glucocorticoids, induces the downstream activation of PI3K, which in turn activates L-type calcium channels. Anti-apoA-1 IgG has been shown to sensitize the L-type calcium channel in a protein kinase A (PKA)-dependent manner. The PI3K and PKA activated pathways alone are not sufficient to induce an increase in basal contraction rate, when simultaneously activated L-type calcium channels are activated, leading to an increase in intracellular Ca²⁺. This signal is amplified by the Na⁺/Ca²⁺ exchanger, leading to an increase of the prepotential slope of the cells, which ultimately translates into an increased contraction rate.