Atherosclerosis最新文献

Background and aims: Peroxisome proliferator-activated receptor α (PPARα) is crucial for regulating cardiac β-oxidation in the heart, liver, and kidney. Ageing can induce cardiac metabolic alterations, but the role of PPARα has not been extensively characterised. The aim of this research was to investigate the role of PPARα in the aged heart.

Methods: Hyperpolarized [1-¹³C]pyruvate was used to evaluate in vivo cardiac carbohydrate metabolism in fed and fasted young (3 months) and old (20-22 months) PPARα knockout (KO) mice versus controls. Cine MRI assessed cardiac structural and functional changes. Cardiac tissue analysis included qRT-PCR and Western blotting for Pparα, medium chain acyl-CoA dehydrenase (MCAD), uncoupling protein (UCP) 3, glucose transporter (GLUT) 4 and PDH kinase (PDK) 1,2, and 4 expression.

Results: PPARα-KO hearts from both young and old mice showed significantly reduced Pparα mRNA and a 58-59 % decrease in MCAD protein levels compared to controls. Cardiac PDH flux was similar in young control and PPARα-KO mice but 96 % higher in old PPARα-KO mice. Differences between genotypes were consistent in fed and fasted states, with reduced PDH flux when fasted. Increased PDH flux was accompanied by a 179 % rise in myocardial GLUT4 protein. No differences in PDK 1, 2, or 4 protein levels were observed between fed groups, indicating the increased PDH flux in aged PPARα-KO mice was not due to changes in PDH phosphorylation.

Conclusions: Aged PPARα-KO mice demonstrated higher cardiac PDH flux compared to controls, facilitated by increased myocardial GLUT4 protein levels, leading to enhanced glucose uptake and glycolysis.

Oxidative stress plays a critical role in numerous pathological processes. Under these stress conditions, the free radical-catalyzed lipid peroxidation generates in vivo a large number of key products that are involved in many physiological and pathophysiological processes. Among these products are neuroprostanes, which arise from the peroxidation of docosahexaenoic acid (DHA), and isoprostanes, resulting from arachidonic acid (AA) and eicosapentaenoic acid (EPA) through the same peroxidation process. These non-enzymatic oxygenated metabolites newly appointed NEO-PUFAs have gained recognition as reliable markers of oxidative stress in neurogenerative and cardiovascular diseases. Moreover, some of them display a wide range of biological activities. The ability to detect and measure these metabolites offers precious insights into the mechanisms of oxidative damage and holds potential therapeutic implications for various health conditions, including neurodegenerative diseases. This review focuses on the role of neuroprostanes as biomarkers for oxidative stress and related diseases, highlighting their potential applications in medical research and treatment.

Cardiovascular disease (CVD) is the leading cause of death worldwide, and despite treatment efforts, cardiovascular function cannot always be restored, and progression of disease be prevented. Critical insights are oftentimes based on tissue samples. Current knowledge of tissue pathology typically relies on invasive biopsies or postmortem samples. Liquid biopsies, which assess circulating mediators to deduce the histology and pathology of distant tissues, have been advancing rapidly in cancer research and offer a promising approach to be translated to the understanding and treatment of CVD. The widely understood elevations in cell-free DNA during acute and chronic cardiovascular conditions, associate with disease, severity, and offer prognostic value. The role of neutrophil extracellular traps (NETs) and circulating nucleases in thrombosis provide a solid rationale for liquid biopsies in CVD. cfDNA originates from various tissue types and cellular sources, including mitochondria and nuclei, and can be used to trace cell and tissue type lineage, as well as to gain insight into the activation status of cells. This article discusses the origin, structure, and potential utility of cfDNA, offering a deeper and less invasive approach for the understanding of the complexities of CVD.

Background and aims: We examined temporal trends and age-related differences in the prevalence of vascular diseases and in their association with ischemic stroke (IS) risk in patients with atrial fibrillation (AF).

Methods: The registry-based FinACAF study covered all patients with AF in Finland during 2007-2018. Incidence rate ratios (IRRs) of IS were computed with Poisson regression, and the interaction of vascular diseases with age and calendar year period was assessed.

Results: We identified 229,565 patients (50.0 % female; mean age 72.7 years) with incident AF. The overall prevalence of any vascular disease was 28.6 %, and the prevalence increased from 2007 to 2018, primarily among patients over 75 years. Overall, 5909 (2.6 %) patients experienced IS within the first year after AF diagnosis. Crude IS rate decreased continuously during the study period in both patients with and without vascular diseases, with the rates remaining consistently higher in patients with vascular diseases. Vascular diseases were independently associated with higher IS incidence among patients under 65 years (adjusted IRR with 95 % confidence interval 1.35 (1.10-1.66)), while among older patients, only peripheral artery disease was associated with IS, and other vascular conditions had no association with IS. No interactions between the calendar year period and vascular diseases with IS rate were observed.

Conclusions: The association between vascular diseases and IS has remained stable over time and vascular diseases were independently associated with higher incidence of IS particularly in patients with AF under the age of 65.

Background and aims: We aimed to investigate the relationship between coronary artery calcium (CAC) density progression and major adverse cardiovascular events (MACE), and the prognostic value of CAC density progression.

Methods: Patients with serial CAC scans were enrolled in this study. CAC density was directly measured in calcified lesions. Change and rate of progression of CAC density were calculated. Cox proportional hazard regression was utilized to estimate hazard ratios (HRs) for time to MACE regarding CAC density. The incremental prognostic value and the reclassification ability of CAC density progression were evaluated using the C-index and continuous net reclassification index (NRI).

Results: 304 patients (57.86 ± 9.47 years, 69.4 % male) were included. There were 47 MACE over a follow-up period of 76.00 (56.00-95.00) months. After adjustment for risk factors and CAC volume, the change of CAC density was inversely associated with MACE (per 10HU: HR: 0.956, 95 % confidence interval: 0.920-0.992, p = 0.018). Adding the change of CAC density to risk factors and baseline CAC density improved the C-index (0.694 vs. 0.678, p = 0.026). Adding the change of CAC density improved reclassification of MACE compared with risk factors and baseline CAC density [NRI = 0.432 (0.016-0.789)].

Conclusions: CAC density progression is inversely associated with MACE. The addition of the change of CAC density improves prognostic value compared to baseline risk factors and CAC density and optimizes risk reclassification.

Cardiovascular diseases (CVD) and their complications continue to be the leading cause of mortality globally. With recent advancements in molecular analytics, individualized treatments are gradually applied to the diagnosis and treatment of CVD. In the field of diagnostics, liquid biopsy combined with modern analytical technologies is the most popular natural source to identify disease biomarkers, as has been successfully demonstrated in the cancer field. While it is not easy to obtain any diseased tissue for different types of CVD such as atherosclerosis, deep vein thrombosis or stroke, liquid biopsies provide a simple and non-invasive alternative to surgical tissue specimens to obtain dynamic molecular information reflecting disease states. The release of cell-free ribonucleic acids (cfRNA) from stressed/damaged/dying and/or necrotic cells is a common physiological phenomenon. CfRNAs are a heterogeneous population of various types of extracellular RNA found in body fluids (blood, urine, saliva, cerebrospinal fluid) or in association with vascular/atherosclerotic tissue, offering insights into disease pathology on a diagnostic front. In particular, cf-ribosomal RNA has been shown to act as a damaging molecule in several cardio-vascular disease conditions. Moreover, such pathophysiological functions of cfRNA in CVD have been successfully antagonized by the administration of RNases. In this review, we discuss the origin, structure, types, and potential utilization of cfRNA in the diagnosis of CVD. Together with the analysis of established CVD biomarkers, the profiling of cfRNA in body fluids may thereby provide a promising approach for early disease detection and monitoring.