RESUMEN
Russian patients with familial hypercholesterolemia (FH) were screened for pathogenic mutations using targeted next generation sequencing. Genetic testing was performed in 52 probands with definite or probable FH based on the Dutch lipid clinic network criteria (DLCN score ≥6). Blood samples were studied by massive parallel sequencing (Illumina HiSeq 1500 platform) using a custom capture library related to dyslipidemia and premature atherosclerosis. Mutations considered to be responsible for monogenic FH were identified in 48% of the probands: 24 with mutations in the LDLR gene and two with a mutation in the APOB gene. There were 22 pathogenic/likely pathogenic mutations in LDLR, eight of which have not been previously described in the literature. Four patients with a clinical picture of homozygous FH had two heterozygous LDLR mutations. Although mutation-negative patients had highly elevated total cholesterol and low-density lipoprotein cholesterol levels, only half of them had a family history of hypercholesterolemia. With respect to heterozygous FH, mutation-positive patients had higher maximum total cholesterol levels (p = 0.01), more severe carotid atherosclerotic lesions, and a higher percentage of premature peripheral artery disease (p = 0.03) than mutation-negative ones. However, the number of patients who suffered from myocardial infarction was similar between the two groups.
RESUMEN
OBJECTIVE: The aim of our investigation was to assess the influence of rosuvastatin therapy and myocardial revascularization on angiogenic growth factors in coronary artery disease patients. METHODS AND RESULTS: Two main groups were examined: group one consisted of patients with successful percutaneous coronary intervention and group two consisted of patients 3 months on rosuvastatin therapy.Vascular endothelial growth factor (VEGF), VEGF receptor Flt-1 (sVEGF-R1) and transforming growth factor beta-1 (TGF-beta1) levels were measured in healthy volunteers and CAD patients before and 6 days after myocardial revascularization.VEGF and basic fibroblast growth factor (bFGF) levels were measured before and 3 months after rosuvastatin therapy, as well as total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC), C-reactive protein (CRP), interleukin 6 (IL-6) and endothelium-dependent vasodilation. VEGF levels did not differ, but beta-TGF levels were significantly lower in CAD patients in comparison with healthy subjects, P < 0.0001. Myocardial revascularization caused changes of VEGF levels from 192.4 +/- 166.1 pg/ml to 264.7 +/- 226.6 pg/ml (P = 0.0066). There were positive changes in lipid levels, lowering of CRP and IL-6 concentrations, improving of endothelial function and decreasing of VEGF levels from 382 +/- 249 pg/ml to 297 +/- 220 pg/ml (P = 0.006) 3 months after rosuvastatin treatment. CONCLUSIONS: There is an elevation of VEGF levels early after myocardial revascularization that may reflect a transient ischaemia and potentially may provoke atherosclerotic plaque neovascularization. Rosuvastatin leads to a decrease of VEGF levels that can be a reflection of the influence on endogenous angiogenesis. There was no correlation between inflammatory factors and VEGF that gives a suggestion about an absence of direct CRP and IL-6 impact on VEGF decreasing during statin treatment.