Suchergebnisse

Transient receptor potential cation channels are emerging as important physiological and therapeutic targets. Within the vanilloid subfamily, transient receptor potential vanilloid 2 (TRPV2) and 4 (TRPV4) are osmo- and mechanosensors becoming critical determinants in cell structure and activity. However, knowledge is scarce regarding how TRPV2 and TRPV4 are trafficked to the plasma membrane or specific organelles to undergo quality controls through processes such as biosynthesis, anterograde/retrograde trafficking, and recycling. This review lists and reviews a subset of protein-protein interactions from the TRPV2 and TRPV4 interactomes, which is related to trafficking processes such as lipid metabolism, phosphoinositide signaling, vesicle-mediated transport, and synaptic-related exocytosis. Identifying the protein and lipid players involved in trafficking will improve the knowledge on how these stretch-related channels reach specific cellular compartments. ; This work was supported by Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme (PIOF-GA-2009-237120 to A.P.-M.), a Universitat Autònoma de Barcelona-Programa Banco de Santander Fellowship, and the Spanish Government grant MINECO BFU2017-87843-R to A.P.-M. P.D.-M. was a recipient of an FI fellowship from Generalitat de Catalunya (FI-2013FIB00251). I.R.D. was supported by the Carlos III Health Institute, co-financed with European Union European Regional Development Funds (CIBERCV CB16/11/00229), and by the Strategic Plan for research and health innovation (PERIS) (SLT006/17/00029).

Abstract Background and Objective Coronary heart disease (CHD) is the leading cause of death, and smoking its strongest modifiable risk factor. Our aim was to determine the impact of the Spanish 2006 partial smoke-free legislation on acute myocardial infarction (AMI) incidence, hospitalization and mortality rates, and 28-day case-fatality in Girona, Spain. Methods Using a population-based registry (the REGICOR Study), we compared population incidence, hospitalization, and mortality rates, and 28-day case-fatality in the pre- and post-ban periods (2002-2005 and 2006-2008, respectively) by binomial regression analysis adjusted for confounding factors. We also analyzed the ban's impact on the outcomes of interest using the AMI definitions of the American Heart Association (AHA)/European Society of Cardiology (ESC) and the World Health Organization (WHO)-Monitoring trends and determinants in cardiovascular diseases (MONICA). Results In the post-ban period, AMI incidence and mortality rates significantly decreased (relative risk [RR] = 0.89; 95% confidence interval [CI] = 0.81-0.97 and RR = 0.82; 95% CI = 0.71-0.94, respectively). Incidence and mortality rates decreased in both sexes, especially in women, and in people aged 65-74 years. Former and non-smokers (passive smokers) showed diminished incidence rates. Implementation of the ban was not associated with AMI case-fatality. Models tended to be more significant with the WHO-MONICA than with the AHA/ESC definition. Conclusions The 2006 Spanish partial smoke-free legislation was associated with a decrease in population AMI incidence and mortality, particularly in women, in people aged 65-74 years, and in passive smokers. These results clarify the association between AMI mortality and the enactment of a partial smoke-free legislation and reinforce the effectiveness of smoking regulations in preventing CHD

In the statin era, the incidence of atherosclerotic cardiovascular diseases (ASCVD) in patients with familial hypercholesterolemia (FH) has not been updated. We aimed to determine the incidence of ASCVD in patients with FH-phenotype (FH-P) and to compare it with that of normal low-density lipoprotein cholesterol (LDL-C) patients. We performed a retrospective cohort study using the Database of the Catalan primary care system, including ≥18-year-old patients with an LDL-C measurement. From 1,589,264 patients available before 2009, 12,823 fulfilled FH-P criteria and 514,176 patients were normolipidemic (LDL-C < 115 mg/dL). In primary prevention, patients with FH-P had incidences of ASCVD and coronary heart disease (CHD) of 14.9/1000 and 5.8/1000 person-years, respectively, compared to 7.1/1000 and 2.1/1000 person-years in the normolipidemic group. FH-P showed hazard ratio (HR) of 7.1 and 16.7 for ASCVD and CHD, respectively, in patients younger than 35 years. In secondary prevention, patients with FH-P had incidences of ASCVD and CHD of 89.7/1000 and 34.5/1000 person-years, respectively, compared to 90.9/1000 and 28.2/1000 person-years in the normolipidemic group (HR in patients younger than 35 years: 2.4 and 6.0). In the statin era, FH-P remains associated with high cardiovascular risk, compared with the normolipidemic population. This excess of risk is markedly high in young individuals ; This project was supported by the Spain'sMinistry of Science and Innovation through the Carlos III Health Institute co-financed with European Union ERDF funds (Network for Prevention and Health Promotion in primary Care (RedIAPP RD16/0007/0004); the Red de Investigación Cardiovascular (RD12/0042/0061, RD12/0042/0013) and CIBERCV; and by the Agency for Management of University and Research Grants of the Generalitat de Catalunya [2017 SGR 1146] and [2017 SGR 222] and through the Agència de Qualitat i Avaluació Sanitàries de Catalunya, Pla estratègic de recerca i innovació en Salut (PERIS) [SLT002/16/00145, SLT006/17/00029]

Risk prediction tools cannot identify most individuals at high coronary artery disease (CAD) risk. Oxidized low-density lipoproteins (oxLDLs) and microRNAs are actively involved in atherosclerosis. Our aim was to examine the association of CAD and oxLDLs-induced microRNAs, and to assess the microRNAs predictive capacity of future CAD events. Human endothelial and vascular smooth muscle cells were treated with oxidized/native low-density lipoproteins, and microRNA expression was analyzed. Differentially expressed and CAD-related miRNAs were examined in serum samples from (1) a case-control study with 476 myocardial infarction (MI) patients and 487 controls, and (2) a case-cohort study with 105 incident CAD cases and 455 randomly-selected cohort participants. MicroRNA expression was analyzed with custom OpenArray plates, log rank tests and Cox regression models. Twenty-one microRNAs, two previously undescribed (hsa-miR-193b-5p and hsa-miR-1229-5p), were up- or down-regulated upon cell treatment with oxLDLs. One of the 21, hsa-miR-122-5p, was also upregulated in MI cases (fold change = 4.85). Of the 28 CAD-related microRNAs tested, 11 were upregulated in MI cases -1 previously undescribed (hsa-miR-16-5p)-, and 1/11 was also associated with CAD incidence (adjusted hazard ratio = 0.55 (0.35-0.88)) and improved CAD risk reclassification, hsa-miR-143-3p. We identified 2 novel microRNAs modulated by oxLDLs in endothelial cells, 1 novel microRNA upregulated in AMI cases compared to controls, and one circulating microRNA that improved CAD risk classification. ; This work was supported by the Spain's Ministry of Science and Innovation (Madrid, Spain), co-financed with European Union European Regional Development Funds –ERDF- (FIS-CP12/03287, FIS-14/00449, FIS-PI081327, INTRASALUD PI11/01801, PI15/00064, IJCI-2016-29393 to DdG-C, CIBERCV (CB16/11/00229, 00246, 00403), CIBERESP CB06/02/0029, CIBEROBN CB06/03/0028); the Spain's ministry of Economy and Competiveness (Madrid, Spain) (BFU2016-75360-R); the BBVA Foundation (Bilbao, Spain) (PR-16-BIO-CAR-0041); the Health Departament of the Generalitat de Catalunya (Barcelona, Spain) through the Agència de Gestió d'Ajuts Universitaris de Recerca de Catalunya (AGAUR) (Barcelona, Spain) (2017SGR222), the Strategic Plan for research and health innovation (PERIS) (Barcelona, Spain) (SLT006/17/00234, SLT002/16/00145, SLT006/17/00029 to IRD); and by the Junta de Castilla y León (Valladolid, Spain) (VA114P17). CIBERs of Pathophysiology of Obesity and Nutrition (CIBEROBN), Cardiovascular Diseases (CIBERCV), and Epidemiology (CIBERESP) are initiatives of the Instituto de Salud Carlos III, Madrid, Spain.