Search

The role of oxidized high- density lipoprotein (oxHDL) and the protective effects of adiponectin in terms of vascular calcification is not well-established. This study was conducted to investigate the effects of oxHDL with regard to inflammation and vascular calcification and to determine the protective role of adiponectin in attenuating the detrimental effects of oxHDL. Cell viability, mineralization, and calcification assays were conducted to optimize the concentration of oxHDL. Then, human vascular smooth muscle cells (HAoVSMCs) were incubated with β-glycerophosphate, HDL, oxHDL, adiponectin, or the combination of oxHDL with adiponectin for 24 h. Protein expression of IL-6, TNF-α, osterix, RUNX2, ALP, type 1 collagen, osteopontin, osteocalcin, WNT-5a, NF-ĸβ(p65), cAMP and STAT-3 were measured by ELISA kits. OxHDL induced vascular calcification by promoting the formation of mineralization nodules and calcium deposits in HAoVSMCs. This was accompanied by an increased secretion of IL-6, osterix, WNT-5a and NF-ĸβ (p65). Interestingly, these detrimental effects of oxHDL were suppressed by adiponectin. Besides, incubation of adiponectin alone on HAoVSMCs showed a reduction of inflammatory cytokines, osteoblastic markers (RUNX2, osterix and osteopontin), WNT-5a and NF-ĸβ (p65). This study exhibits the ability of oxHDL in inducing inflammation and vascular calcification and these detrimental effects of oxHDL can be attenuated by adiponectin.

PubMed: 30270054, 2-s2.0-85053666909, Background and aims: Management of familial hypercholesterolaemia (FH) may vary across different settings due to factors related to population characteristics, practice, resources and/or policies. We conducted a survey among the worldwide network of EAS FHSC Lead Investigators to provide an overview of FH status in different countries. Methods: Lead Investigators from countries formally involved in the EAS FHSC by mid-May 2018 were invited to provide a brief report on FH status in their countries, including available information, programmes, initiatives, and management. Results: 63 countries provided reports. Data on FH prevalence are lacking in most countries. Where available, data tend to align with recent estimates, suggesting a higher frequency than that traditionally considered. Low rates of FH detection are reported across all regions. National registries and education programmes to improve FH awareness/knowledge are a recognised priority, but funding is often lacking. In most countries, diagnosis primarily relies on the Dutch Lipid Clinics Network criteria. Although available in many countries, genetic testing is not widely implemented (frequent cost issues). There are only a few national official government programmes for FH. Under-treatment is an issue. FH therapy is not universally reimbursed. PCSK9-inhibitors are available in ?2/3 countries. Lipoprotein-apheresis is offered in ?60% countries, although access is limited. Conclusions: FH is a recognised public health concern. Management varies widely across countries, with overall suboptimal identification and under-treatment. Efforts and initiatives to improve FH knowledge and management are underway, including development of national registries, but support, particularly from health authorities, and better funding are greatly needed. © 2018 Elsevier B.V., Universidade de São Paulo, USP European Atherosclerosis Society, EAS Amgen Merck Sharp and Dohme, MSD, The ELSA Study suggests heterozygous FH (HeFH) may affect 1:263 Brazilians (?766,000 individuals). Currently, the only active genetic cascade screening program in Brazil is Hipercol Brasil in Sao Paulo (genetic testing for adults with low-density lipoprotein cholesterol (LDL-C) ?230?mg/dL, to maximise cost-effectiveness), with 1719 heterozygotes, 25 homozygotes, 13 compound-heterozygotes and one double-heterozygote identified by March 2018. To date, 4340 individuals from 440 families were screened. Genetic testing is funded by a government tax reduction programme (PROADI-SUS), and cascade screening by partnering between Samaritano Hospital and Heart Institute (InCor) University of Sao Paulo. Most FH patients are under non-specialist care and currently under-treated., Prevalence is unknown but assumed at 1:250. There is no state programme and few patients were diagnosed before the Latvian FH Registry was established in 2015. To date, the Registry has identified 181 cases (2.3% of 7876 estimated HeFH cases; no HoFH). Cascade screening is performed in first-degree relatives of index cases with probable/definite FH. Genetic testing is not reimbursed but has been funded by research grants for a few patients/relatives. About 5% of patients had LDL-C at target before inclusion in the Registry [ 61 ]. Statins are reimbursed 50% in primary prevention; statins and ezetimibe, 75–100% in secondary prevention; PCSK9i are available, but not reimbursed., Estimated prevalence is 1:250 (based on a meta-analysis of 6 observational studies) or 136,300 adults (only 2% diagnosed) [ 69 , 70 ]. Based on LIPIDOGRAM studies (2004–2015, ?50,000 participants), prevalence might be?1:200 [ 71 , 72 ]. Five HoFH cases are described [ 73 , 74 ]. Patients with DLCN ?3 are referred for genetic testing, funded by the National Health Program. The National Centre for FH at University Clinical Hospital, Medical University of Gdansk, was established in 2017, financed by the Ministry of Health. From August 2017, 345 patients underwent genetic testing (153 positive, including 46 relatives; 1 HoFH). Since 1999, 1884 patients (562 families) have undergone genetic testing and cascade diagnosis (data from the National Polish FH Registry, Medical University of Gdansk, established in 2000). PCSK9i are not reimbursed (under discussion with the Ministry of Health)., The EAS FHSC project has received support from a Pfizer Independent Grant for Learning & Change 2014 (No: 16157823 ) and from investigator-initiated unrestricted research grants to the European Atherosclerosis Society from Amgen , MSD , and Sanofi-Aventis .