Role of Lipoprotein A in Lower Extremity Peripheral Artery Disease

Lipoprotein A (Lp[a]) is a low-density lipoprotein (LDL)-like particle consisting of an apolipoprotein(a) particle attached to an apolipoprotein B-100 molecule, the apolipoprotein in LDL, by way of a single covalent disulfide bond. 1 Shah NP Pajidipati NJ McGarrah RW Navar AM Vemulapalli S Blazing MA Shah SH Hernandez AF Patel MR. Lipoprotein (a): an Update on a Marker of Residual Risk and Associated Clinical Manifestations. Am J Cardiol. 2020; 126: 94-102 Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar The apo(a) component bears homology to plasminogen and has been shown to inhibit fibrinolysis and potentiate vascular thrombosis, stenosis, and thromboembolization. 2 Tsimikas S. A Test in Context: lipoprotein(a): diagnosis, prognosis, controversies, and emerging therapies. J Am Coll Cardiol. 2017; 69: 692-711 Crossref PubMed Scopus (600) Google Scholar Furthermore, the apo(a) portion of Lp(a) is believed to attract oxidized phospholipids that promote endothelial dysfunction, inflammation, and vascular calcification. 3 Narula N Dannenberg AJ Olin JW Bhatt DL Johnson KW Nadkarni G Min J Torii S Poojary P Anand SS Bax JJ Yusuf S Virmani R Narula J. Pathology of peripheral artery disease in patients with critical limb ischemia. J Am Coll Cardiol. 2018; 72: 2152-2163 Crossref PubMed Scopus (157) Google Scholar Based on these characteristics of the apo(a) molecule, Lp(a) is endowed with proatherogenic, thrombotic, and proinflammatory properties. 2 Tsimikas S. A Test in Context: lipoprotein(a): diagnosis, prognosis, controversies, and emerging therapies. J Am Coll Cardiol. 2017; 69: 692-711 Crossref PubMed Scopus (600) Google Scholar These features of Lp(a) correspond well with the pathophysiology of lower extremity (LE) peripheral artery disease (PAD) that is largely driven by thrombosis and thromboembolism rather than plaque rupture. 3 Narula N Dannenberg AJ Olin JW Bhatt DL Johnson KW Nadkarni G Min J Torii S Poojary P Anand SS Bax JJ Yusuf S Virmani R Narula J. Pathology of peripheral artery disease in patients with critical limb ischemia. J Am Coll Cardiol. 2018; 72: 2152-2163 Crossref PubMed Scopus (157) Google Scholar Lp(a) levels are highly heritable, genetically determined, and may not only be a marker of atherosclerotic cardiovascular disease (ASCVD) risk but also have an important pathophysiologic role in the development of atherosclerosis. 4 Marsche G. Lp-PLA2, plaque inflammation and lesion development vary fundamentally between different vascular sites. J Am Heart Assoc. 2015; 4e001800 Crossref Scopus (8) Google Scholar