Background: α1PDX and serpin B8 are proprotein convertase (PC) inhibitors whose specificity and selectivity for PCs are not understood. Results: α1PDX-serpin B8 and furin-PC chimeras revealed new serpin and protease (re)active-site and exosite determinants of reactivity. Conclusion: α1PDX reactive-site and exosite determinants may be exploited for engineering specificity and selectivity for inh...

In this issue of Circulation, van der Graaf and colleagues1 studied 1430 children, aged 4 to 18 years, who were referred to an academic pediatric lipid clinic in the Netherlands because of dyslipidemia from July 1989 to January 2008. The objective was to determine what proportion of those with the phenotype of autosomal dominant hypercholesterolemia (ADH) had mutations in the genes encoding the...

PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibition is an effective therapy to reduce low-density lipoprotein cholesterol and cardiovascular events. A recent study shows that 1 or 2 doses of inclisiran, a long-acting synthetic small-interfering RNA that selectively targets hepatic PCSK9, causes a sustained reduction of plasma low-density lipoprotein cholesterol for ≤6 months. Pendi...

Non-synonymous mutations affecting both alleles of PCSK1 (proprotein convertase 1/3) are associated with obesity and impaired prohormone processing. We report a proband who was compound heterozygous for a maternally inherited frameshift mutation and a paternally inherited 474kb deletion that encompasses PCSK1, representing a novel genetic mechanism underlying this phenotype. Although pro-vasopr...

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant disorder that affects cholesterol metabolism and is an important risk factor for heart disease. Three different genes were causally linked to this disorder: LDLR (low density lipoprotein receptor), APOB [apolipoprotein B (including Ag(x) antigen)], and PCSK9 (proprotein convertase subtilisin/kexin type 9). We evaluated a ne...

PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibition is an effective therapy to reduce low-density lipoprotein cholesterol and cardiovascular events. A recent study shows that 1 or 2 doses of inclisiran, a long-acting synthetic small-interfering RNA that selectively targets hepatic PCSK9, causes a sustained reduction of plasma low-density lipoprotein cholesterol for ≤6 months. Pendi...

A fluorescence-based enzyme activity assay has been demonstrated within a small-core microstructured optical fiber (MOF) for the first time. To achieve this, a reflection-based automated alignment system has been developed, which uses feedback and piezoelectric actuators to maintain optical alignment. The auto-alignment system provides optical stability for the time required to perform an activ...