Lp(a) in the Pathogenesis of Aortic Stenosis and Approach to Therapy with Antisense Oligonucleotides or Short Interfering RNA

Figure 1. Prognosis of symptomatic patients with severe aortic stenosis in the absence of specific treatment (modified from Ross and Braunwald [4]). y, years.

Figure 2. The pathogenetic mechanism of aortic valve stenosis: dyslipidemia, inflammation, and calcification. The figure summarizes the main pathways involved in the aortic valve calcification process. Lp(a), lipoprotein(a); LDL, low-density lipoprotein; eNOS, endothelial nitric oxide synthase; ROS, reactive oxygen species; OxPL, oxidized phospholipids; OxLDL, oxidized LDL; LpPLA2, lipoprotein-associated phospholipase A2; LysoPC, lysophosphatidylcholine; ATX, autotaxin; LysoPA, lysophosphatidic acid; AA, arachidonic acid; COX2, cyclooxygenase-2; 5LO, 5-lipoxygenase; MMP, matrix metalloproteinases; TIMP, tissue inhibitor of metalloprotease; TNF, tumor necrosis factor; IL1, interleukin-1; IL6, interleukin-6; VEGF, vascular endothelial growth factor; ACE, angiotensin converting enzyme; BMP2, bone morphogenetic protein 2; RUNX2, runt-related transcription factor 2; MSX2, Msh Homeobox 2; RANKL, receptor activator of nuclear factor κB Ligand; ENPP1, ectonucleotide pyrophosphatase/phosphodiesterase I; NT5E, ecto-5′-nucleotidase; ALP, alkaline phosphatase.

Figure 3. Flow chart for severe aortic stenosis treatment, according to VHD ESC guidelines 2021. In the figure, the green boxes indicate class I of recommendation, and the yellow boxes indicate class IIa of recommendation. The red box groups all conditions that need to be assessed by the heart team. V, aortic valve peak velocity; G, aortic valve mean gradient; AVA, aortic valve area; LVEF, left ventricular ejection fraction; Svi, systolic volume index; ETT, exercise tolerance test; BP, blood pressure; CCT, Cardiac Computed Tomography; BNP, brain natriuretic peptide; AVR, aortic valve implantation; TAVI, transcatheter aortic valve replacement.