Statins are currently the major therapeutic strategies to lower low-density lipoprotein cholesterol
(LDL-C) levels. However, a number of hypercholesterolemia patients still have a residual cardiovascular
disease (CVD) risk despite taking the maximum-tolerated dose of statins. Proprotein convertase
subtilisin/kexin type 9 (PCSK9) binds to low-density lipoprotein receptor (LDLR), inducing its
degradation in the lysosome and inhibiting LDLR recirculating to the cell membranes. The gain-offunction
mutations in PCSK9 elevate the LDL-C levels in plasma. Therefore, PCSK9 inhibitors become
novel therapeutic approaches in the treatment of hypercholesterolemia. Several PCSK9 inhibitors
have been under investigation, and much progress has been made in clinical trials, especially for
monoclonal antibodies (MoAbs). Two MoAbs, evolocumab and alirocumab, are now in clinical use. In
this review, we summarize the development of PCSK9 inhibitors, including antisense oligonucleotides
(ASOs), small interfering RNA (siRNA), small molecule inhibitor, MoAbs, mimetic peptides and
adnectins, and the related safety issues.
D012 Development of novel therapeutic strategies to stimulate revascularization in heart failure: biopolymeric delivery of a synergistic combination of angiogenic growth factors