Lipoprotein [a] is cleared from the plasma primarily by the liver in a process mediated by apolipoprotein [a]

The cellular and molecular mechanisms responsible for lipoprotein [ a] (Lp[a]) catabolism are unknown. We examined the plasma clearance of Lp[ a] and LDL in mice using lipoproteins isolated from human plasma coupled to radiolabeled tyramine cellobiose. Lipoproteins were injected into wild-type, LDL receptor-deficient (Ldlr(-/-)), and apolipoprotein E-deficient (Apoe(-/-)) mice. The fractional catabolic rate of LDL was greatly slowed in Ldlr(-/-) mice and greatly accelerated in Apoe(-/-) mice compared with wild-type mice. In contrast, the plasma clearance of Lp[ a] in Ldlr(-/-) mice was similar to that in wild-type mice and was only slightly accelerated in Apoe(-/-) mice. Hepatic uptake of Lp[ a] in wild-type mice was 34.6% of the injected dose over a 24 h period. The kidney accounted for only a small fraction of tissue uptake (1.3%). To test whether apolipoprotein [ a] (apo[a]) mediates the clearance of Lp[a] from plasma, we coinjected excess apo[a] with labeled Lp[ a]. Apo[a] acted as a potent inhibitor of Lp[ a] plasma clearance. Asialofetuin, a ligand of the asialoglycoprotein receptor, did not inhibit Lp[ a] clearance. In summary, the liver is the major organ accounting for the clearance of Lp[ a] in mice, with the LDL receptor and apolipoprotein E having no major roles. Our studies indicate that apo[a] is the primary ligand that mediates Lp[a] uptake and plasma clearance

Treatment of degenerative mitral regurgitation in elderly patients

Advanced age is a common contraindication for cardiac surgery, particularly in high-risk patients with comorbidities, such as pulmonary and renal impairment, associated coronary artery disease, and neurological disorders. In elderly patients with degenerative mitral regurgitation who are not eligible for conventional surgical valve repair or replacement, percutaneous valve repair is emerging as a viable alternative therapeutic option. Nonsurgical and minimally invasive therapies for degenerative mitral regurgitation are of particular value in this subset of patients, because these interventions are associated with reduced perioperative mortality, clinical improvement, and faster recovery than is possible with surgical procedures. However, given that surgery remains the gold-standard treatment and should still be considered an option regardless of a patient's age, transcatheter mitral valve repair should be performed only in candidates who will gain the most benefit from it. The balance between the risks and benefits, and the value versus the futility of procedures to treat degenerative mitral regurgitation in elderly patients should be assessed by a specialized multidisciplinary care team. In this Review, we discuss the treatment options and indications for degenerative mitral regurgitation in elderly patients