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Current Medicinal Chemistry Jun 2024Tripartite-motif protein family member 65 (TRIM65) belongs to the tripartite motif (TRIM) protein family. Its typical structure consists of the RING, B-Box motif, and...
Tripartite-motif protein family member 65 (TRIM65) belongs to the tripartite motif (TRIM) protein family. Its typical structure consists of the RING, B-Box motif, and coiled-coil domains, which are highly conserved at the N-terminus and the variable SPRY domain at the C-terminus. TRIM65 is an E3 ubiquitin ligase that participates in physiological and pathological processes through the ubiquitination pathway, including intracellular signal transduction, protein degradation, cell proliferation, apoptosis, carcinogenesis, autophagy, and phenotypic transformation. Evidence shows that TRIM65 plays a remarkable and obscure role in diseases, including multisystem tumours, neurodegenerative diseases, immune system diseases, and inflammatory diseases. This review is devoted to elaborating on the relationship between TRIM65 and diseases and its pathogenic mechanism, providing a theoretical basis for TRIM65 as a possible pathogenic target of diseases and exploring the possible future research direction of TRIM65 and the challenges it may face.
PubMed: 38939997
DOI: 10.2174/0109298673304966240614091547 -
Circulation. Genomic and Precision... Jun 2024Clonal hematopoiesis of indeterminate potential (CHIP) occurs due to acquired mutations in bone marrow progenitor cells. CHIP confers a 2-fold risk of atherosclerotic...
BACKGROUND
Clonal hematopoiesis of indeterminate potential (CHIP) occurs due to acquired mutations in bone marrow progenitor cells. CHIP confers a 2-fold risk of atherosclerotic cardiovascular disease. However, there are limited data regarding specific cardiovascular phenotypes. The purpose of this study was to define the coronary artery disease phenotype of the CHIP population-based on coronary angiography.
METHODS
We recruited 1142 patients from the Vanderbilt University Medical Center cardiac catheterization laboratory and performed DNA sequencing to determine CHIP status. Multivariable logistic regression models and proportional odds models were used to assess the association between CHIP status and angiography phenotypes.
RESULTS
We found that 18.4% of patients undergoing coronary angiography had a CHIP mutation. Those with CHIP had a higher risk of having obstructive left main (odds ratio, 2.44 [95% CI, 1.40-4.27]; =0.0018) and left anterior descending (odds ratio, 1.59 [1.12-2.24]; =0.0092) coronary artery disease compared with non-CHIP carriers. We additionally found that a specific CHIP mutation, ten eleven translocase 2 ), has a larger effect size on left main stenosis compared with other CHIP mutations.
CONCLUSIONS
This is the first invasive assessment of coronary artery disease in CHIP and offers a description of a specific atherosclerotic phenotype in CHIP wherein there is an increased risk of obstructive left main and left anterior descending artery stenosis, especially among mutation carriers. This serves as a basis for understanding enhanced morbidity and mortality in CHIP.
PubMed: 38939956
DOI: 10.1161/CIRCGEN.123.004415 -
Exploration (Beijing, China) Jun 2024Atherosclerosis, a chronic disease associated with metabolism, poses a significant risk to human well-being. Currently, existing treatments for atherosclerosis lack... (Review)
Review
Atherosclerosis, a chronic disease associated with metabolism, poses a significant risk to human well-being. Currently, existing treatments for atherosclerosis lack sufficient efficiency, while the utilization of surface-modified nanoparticles holds the potential to deliver highly effective therapeutic outcomes. These nanoparticles can target and bind to specific receptors that are abnormally over-expressed in atherosclerotic conditions. This paper reviews recent research (2018-present) advances in various ligand-modified nanoparticle systems targeting atherosclerosis by specifically targeting signature molecules in the hope of precise treatment at the molecular level and concludes with a discussion of the challenges and prospects in this field. The intention of this review is to inspire novel concepts for the design and advancement of targeted nanomedicines tailored specifically for the treatment of atherosclerosis.
PubMed: 38939861
DOI: 10.1002/EXP.20230090 -
JACC. Advances Apr 2024Cost-effectiveness of testing for coronary artery calcium (CAC) relative to other treatment strategies is not established in Canada.
BACKGROUND
Cost-effectiveness of testing for coronary artery calcium (CAC) relative to other treatment strategies is not established in Canada.
OBJECTIVES
The purpose of this study was to evaluate the cost-effectiveness of using CAC score-guided statin treatment compared with universal statin therapy among intermediate-risk, primary prevention patients eligible for statins.
METHODS
A state transition, microsimulation model used data from Canadian sources and the Multi-Ethnic Study of Atherosclerosis to simulate clinical and economic consequences of cardiovascular disease from a Canadian publicly funded health care system perspective. In the CAC score-guided treatment arm, statins were started when CAC ≥1. Outcome of interest was the incremental cost-effectiveness ratio at 5 and 10 years; an incremental cost-effectiveness ratio <$50,000 per quality-adjusted life year (QALY) gained was considered cost-effective. Sensitivity analyses examined uncertainty in model parameters.
RESULTS
Compared with universal statin treatment at 5 and 10 years, CAC score-guided statin treatment was projected to increase mean costs by $326 (95% CI: $325-$326) and $172 (95% CI: $169-$175), increase mean QALYs by 0.01 (95% CI: 0.01-0.01) and 0.02 (95% CI: 0.02-0.02), and cost $54,492 (95% CI: $52,342-$56,816) and $8,118 (95% CI: $7,968-$8,279) per QALY gained, respectively. The model was most sensitive to statin cost, CAC testing cost, adherence to statin monitoring, and disutility associated with daily statin use. At 5 years, CAC score-guided statin treatment was cost-effective when CAC test costs ranged from $80 to $160 in different scenarios.
CONCLUSIONS
CAC score-guided statin initiation in comparison to universal statin treatment was borderline cost-neutral at 5 years and cost-effective at 10 years in statin-eligible Canadian patients at intermediate cardiovascular disease risk.
PubMed: 38939688
DOI: 10.1016/j.jacadv.2024.100886 -
JACC. Advances May 2024
PubMed: 38939635
DOI: 10.1016/j.jacadv.2024.100933 -
JACC. Advances Aug 2023
PubMed: 38939429
DOI: 10.1016/j.jacadv.2023.100444 -
JACC. Advances Feb 2024
PubMed: 38939384
DOI: 10.1016/j.jacadv.2023.100756 -
JACC. Advances Feb 2024
PubMed: 38939380
DOI: 10.1016/j.jacadv.2023.100788 -
JACC. Advances Feb 2024The initiation of coronary artery calcium (CAC) is an important physiologic milestone associated with increased cardiovascular disease risk. However, traditional risk...
BACKGROUND
The initiation of coronary artery calcium (CAC) is an important physiologic milestone associated with increased cardiovascular disease risk. However, traditional risk factors (RF) do not perform well for predicting incident CAC among the 54 million older U.S. adults.
OBJECTIVES
The authors sought to assess the association between nontraditional cardiovascular disease RF and incident CAC in older persons.
METHODS
There were 815 MESA (Multi-Ethnic Study of Atherosclerosis) participants ≥65 years of age who had CAC = 0 at Visit 1 and a follow-up CAC scan. Multivariable adjusted Cox hazards ratios (aHR) and C-statistics were calculated to examine the association of nontraditional RF with incident CAC.
RESULTS
The mean age was 70.2 years and 67% were women. The median follow-up time to repeat CAC scan was 3.6 years (IQR: 2.6-9.2 years) and 45% of participants developed incident CAC. Albuminuria (aHR: 1.50, 95% CI: 1.07-2.09), carotid plaque (aHR: 1.32, 95% CI: 1.04-1.66), and thoracic aortic calcification (TAC) (aHR: 1.38, 95% CI: 1.10-1.75) were significantly associated with incident CAC, while higher levels of nontraditional RF including apolipoprotein-B, lipoprotein(a), high-sensitivity troponin T, and N-terminal pro-brain natriuretic peptide were not. When added to demographics, albuminuria, carotid plaque, and TAC provided a greater C-statistic improvement (+0.047, = 0.004) vs all traditional RF combined (+0.033, = 0.05).
CONCLUSIONS
Among nontraditional RF and measures of subclinical atherosclerosis, only albuminuria, carotid plaque, and TAC were significantly associated with incident CAC in persons ≥65 years of age. Identification of albuminuria or extracoronary atherosclerosis may help guide the timing of repeat CAC scoring in older persons with baseline CAC = 0.
PubMed: 38939371
DOI: 10.1016/j.jacadv.2023.100755 -
JACC. Advances Jun 2024
PubMed: 38938864
DOI: 10.1016/j.jacadv.2024.100939