PCSK9 Plasma Levels Are Associated with Mechanical Vascular Impairment in Familial Hypercholesterolemia Subjects without a History of Atherosclerotic Cardiovascular Disease: Results of Six-Month Add-On PCSK9 Inhibitor Therapy

被引：13

作者：

Toscano, Arianna ^{[1
]}

Cinquegrani, Maria ^{[1
]}

Scuruchi, Michele ^{[1
]}

Di Pino, Antonino ^{[2
]}

Piro, Salvatore ^{[2
]}

Ferrara, Viviana ^{[2
]}

Morace, Carmela ^{[1
]}

Lo Gullo, Alberto ^{[3
]}

Imbalzano, Egidio ^{[1
]}

Purrello, Francesco ^{[2
]}

Squadrito, Giovanni ^{[1
]}

Scicali, Roberto ^{[2
]}

Mandraffino, Giuseppe ^{[1
]}

机构：

[1] Univ Messina, Dept Clin & Expt Med, Internal Med Unit, Lipid Ctr, I-98122 Messina, Italy

[2] Univ Catania, Dept Clin & Expt Med, I-95124 Catania, Italy

[3] ARNAS Garibaldi Hosp, Dept Med, Unit Rheumatol, I-95122 Catania, Italy

来源：

BIOMOLECULES | 2022年 / 12卷 / 04期

关键词：

PCSK9; familial hypercholesterolemia; atherosclerotic injury; SUBTILISIN/KEXIN TYPE 9; PULSE-WAVE VELOCITY; STATIN THERAPY; DOSE ATORVASTATIN; LDL CHOLESTEROL; PROPROTEIN; EZETIMIBE; IMPACT; ROSUVASTATIN; INFLAMMATION;

D O I：

10.3390/biom12040562

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Proprotein convertase subtilisin/kexin type-9 (PCSK9) is a key regulator of low-density lipoprotein (LDL) metabolism involved in the degradation of the low-density lipoprotein receptor (LDLR) through complex mechanisms. The PCSK9 plasma levels change according to lipid lowering therapy (LLT). Few data exist regarding the role of PCSK9 in vascular damage. We aimed to evaluate the impact of PCSK9 plasma levels on pulse wave velocity (PWV) and the effect of PCSK9 inhibitors (PCSK9-i) on circulating PCSK9 and PWV in a cohort of heterozygous familial hypercholesterolemia (HeFH) subjects. In a previous step, HeFH patients were enrolled and LLT was prescribed according to guidelines. Biochemical analyses and PWV assessment were performed at baseline (T0), after 6 months of high-efficacy statin plus ezetimibe (T1) and after 6 months of PCSK9-i (T2). The PCSK9 levels were evaluated in 26 selected HeFH subjects at the three time points and 26 healthy subjects served as controls for the reference value for PCSK9 plasma levels. The PWV values decreased at each time point in HeFH subjects after LLT starting (8.61 +/- 2.4 m/s, -8.7%; p < 0.001 vs. baseline at T1, and 7.9 +/- 2.1 m/s, -9.3%; p < 0.001 vs. both T1 and baseline) and it was correlated to PCSK9 (r = 0.411, p = 0.03). The PCSK9 levels increased on statin/EZE therapy (+42.8% at T1) while it decreased after PCSK9-i was started (-34.4% at T2). We noted a significant relationship between PCSK9 levels and PWV changes at T1 and T2. In conclusion, PCSK9 levels were associated with baseline PWV values in HeFH subjects; moreover, we found that PCSK9 level variations seemed to be correlated with PWV changes on LLT. A longer observation time and wider sample size are needed to assess the potential role of PCSK9 plasma levels on the vascular function and remodelling, and to clarify the effects of PCSK9-i in these pathways.

引用

页数：13

共 51 条

[1] Effect of Evolocumab on Lipoprotein(a) and PCSK9 in Healthy Individuals with Elevated Lipoprotein(a) Level [J].