Possible involvement of PCSK9 overproduction in hyperlipoproteinemia associated with hepatocellular carcinoma: A case report

Herein, we describe a 69-year-old Japanese man with massive type III hyperlipoproteinemia (total cholesterol, 855 mg/dL; triglyceride, 753 mg/dL) presenting as a paraneoplastic manifestation of hepatitis B virus–associated hepatocellular carcinoma. The messenger RNA expression of sterol regulatory element–binding protein-2 and proprotein convertase subtilisin/kexin 9 in the tumor tissue was increased by 13-fold and 4-fold, respectively, compared with the non-tumor tissue. Serum level of active form of PCSK9 was 382 ng/mL (reference range: 253 ± 79 ng/mL). The non-tumor tissue had extremely low expression of low-density lipoprotein receptor and low-density lipoprotein receptor–related protein 1. Together, we speculate that marked overexpression of sterol regulatory element–binding protein-2 in the tumor may stimulate the secretion of PCSK9, which inhibits the lipoprotein receptors in the non-tumor tissue, thereby causing paraneoplastic hyperlipoproteinemia.     

两种高密度脂蛋白胆固醇均相测定法的临床评价

目的对选择性抑制法(PPD法)和PEG修饰法(PEGME法)两种高密度脂蛋白胆固醇(HDL-C)均相测定法进行临床评价。方法将上述两种方法与传统的磷钨酸镁沉淀法(PTA-Mg2 法)进行比较,分析各自的精密度、准确性、特异性和干扰因素。结果上述两种均相测定法均具有较好的精密度(批内、日间及总变异系数均小于4%),两均相法与PTA-Mg2 法(X)具有良好相关性犤PPD法(Y):Y=0.9316X 0.1063,相关系数r=0.9762;PEGME法(Y):Y=0.9106X 0.1368,r=0.9894犦。两法线性范围均较宽(线性均至4.14mmol/L),最低检测浓度均为0.08mmol/L,回收率为94.1%～106.2%。两均相法基本不受极低密度脂蛋白、低密度脂蛋白和血红蛋白的影响(偏差均小于5%),甘油三酯浓度在17.0mmol/L以下对两法基本无影响,胆红素高于200mg/L时可使两法测定结果偏低。结论两种HDL-C均相测定法简便、快速、结果准确,易于自动分析,适合在临床实验室常规检测应用。     

SERUM LIPIDS AND LIPOPROTEINS IN 157 INSULIN DEPENDENT DIABETIC CHILDREN AND ADOLESCENTS IN RELATION TO METABOLIC REGULATION, OBESITY AND GENETIC HYPERLIPOPROTEINEMIA

ABSTRACT. Serum lipids and lipoproteins were measured in 157 insulin dependent diabetic children and adolescents (IDDM) and in 350 healthy reference individuals. Serum triglyceride values were lower and total cholesterol and high density lipoprotein cholesterol higher in IDDM. Metabolic regulation reflected by glucosuria, postprandial blood glucose, number of hypoglycemic episodes and hemoglobin AIC all correlated strongly with serum triglyceride and very low density lipoprotein cholesterol but not with serum low density lipoprotein cholesterol or high density lipoprotein cholesterol. Serum lipids and lipoproteins did not correlate with obesity. Three children had genetic hyperlipoproteinemia.
In IDDM measurement of serum lipids and lipoproteins can thus be used to further assess metabolic regulation. Measurement of serum lipids and lipoproteins seems warranted for future evaluation of the risk of cardiovascular disease in IDDM.     

Platelet function and antithrombins in hyperlipoproteinemia type IIa

Platelet function was studied in 35 patients with type IIa hyperlipoproteinemia and 22 normal controls. Platelet aggregation by ADP in concentrations ranging from 2×10^?6 to 2×10^?5 M, and adrenaline 10^?6 M were similar in both groups. In contrast, aggregation induced by collagen and secondary aggregation elicited by bovine factor VIII were significantly lower in hypercholesterolemic patients, who also disclosed an increased plasmatic antiheparin activity. This plasmatic antiheparin activity was inversely correlated to plasmatic cholesterol concentration, (r = ?0.50, p<0.01). PF3 and PF4 were normal in patients with type IIa hyperlipoproteinemia. AntiFXa, antithrombin III, and heparin cofactor were also determined. Heparin cofactor was found to be significantly lower in hypercholesterolemic patients than in controls, and inversely correlated to plasmatic cholesterol concentration (r = ?0.51, p<0.05). These observations suggest that the thrombotic tendency in hypercholesterolemia may be related to a decrease of plasmatic heparin cofactor.     

CHRONIC RENAL FAILURE—TRIGLYCERIDES AND DEGENERATIVE DISEASE

Hypertriglyceridemia with type IV hyperlipoproteinemia is a common finding in more than 40 percent of patients with chronic renal failure prior to entry into chronic hemodialysis programs. These patients show an accelerated rate of development of degenerative vascular disease in coronary and cerebral vessels once they begin hemodialysis.     

REGRESSION AND PROGRESSION OF FEMORAL ATHEROSCLEROSIS IN HUMAN BEINGS TREATED FOR HYPERLIPOPROTEINEMIA

Nine of 22 patients demonstrated regression of atherosclerotic lesions in their femoral arteries when they were treated with diet and drugs to control their hyperlipoproteinemic states. The patients had no symptoms of claudication, yet they had demonstrable atherosclerotic lesions in their femoral artery prior to study.     

Isoprostane 8-epi-PGF2alpha is frequently increased in patients with muscle pain and/or CK-elevation after HMG-Co-enzyme-A-reductase inhibitor therapy

BACKGROUND: Muscle pains with or without CK-elevation are among the most frequently observed side-effects in patients with hyperlipoproteinemia on various statins. The pathophysiological background, however, remains obscure. METHODS: We examined isoprostane 8-epi-PGF2alpha, a marker of in-vivo oxidation injury, in plasma, serum and urine in these patients at baseline, when muscle problems manifested and different time intervals after withdrawing the respective statin. A healthy control group and a group of untreated patients with hyperlipoproteinemia were run as controls. RESULTS: The majority of patients with muscular side-effects show elevated 8-epi-PGF2alpha in plasma and urine, whereas serum values were elevated only to a lesser extent. Stopping statin therapy or successfully changing to another member of this family of compounds resulted in a normalization of the values in all patients. CONCLUSION: These findings indicate a significant involvement of oxidative injury in the muscular side-effects of statins in patients suffering from hyperlipoproteinemia.     

血清中apoA-Ⅰ/apoB-100比值测定的结果分析

目的 :血清中 apo A- / apo B- 10 0比值的测定用于心血管疾病的诊断及预防。方法 :用比浊免疫测定法对12 0例临床确诊的高脂血症患者及 30例正常健康人血清进行 apo A- / apo B- 10 0比值测定 ,对结果进行分析。结果 :高脂血症患者血清 apo A- / apo B- 10 0明显低于正常组 (P<0 ,0 1)。结论 :apo A- / apo B- 10 0比值的测定对于早期诊断及预防高脂血症所致的心血管疾病有重要参考价值