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JACC. Advances Nov 2023The prevalence and degree of lower extremity artery disease in hemodialysis (HD) patients is higher than in the general population. However, the pathological features...
BACKGROUND
The prevalence and degree of lower extremity artery disease in hemodialysis (HD) patients is higher than in the general population. However, the pathological features have not yet been evaluated.
OBJECTIVES
The aim of the study was: 1) to compare lesion characteristics of lower extremity artery disease in HD vs non-HD patients; and 2) to determine factors associated with severe medial calcification.
METHODS
Seventy-seven lower limb arteries were assessed from 36 patients (median age 77 years; 23 men; 21 HD and 15 non-HD) who underwent autopsy or lower limb amputation. Arteries were serially cut at 3- to 4-mm intervals creating 2,319 histological sections. Morphometric analysis and calcification measurements were performed using ZEN software. Calcification with a circumferential angle (arc) ≥180° was defined as severe calcification. Multivariable logistic regression was used to identify risk factors for severe medial calcification.
RESULTS
The degree of the medial calcification arc was significantly higher in the HD group compared to the non-HD group ( < 0.0001). In the multivariable analysis, HD was associated with severe medial calcification in below-the-knee lesions (OR: 17.1; = 0.02). The degree of intimal calcification in above-the-knee lesions was also significantly higher in HD patients with a higher prevalence of advanced atherosclerotic plaque ( = 0.02). The prevalence of severe bone formation was more common in the HD patients ( = 0.01).
CONCLUSIONS
Hemodialysis patients demonstrated a higher degree of medial and intimal calcification compared with non-HD patients. The difference was more prominent in the medial calcification of below-the-knee lesions.
PubMed: 38938733
DOI: 10.1016/j.jacadv.2023.100656 -
JACC. Advances Nov 2023Heterozygous familial hypercholesterolemia (HeFH) is a monogenic disorder characterized by increased circulating low-density lipoprotein cholesterol and accelerated...
BACKGROUND
Heterozygous familial hypercholesterolemia (HeFH) is a monogenic disorder characterized by increased circulating low-density lipoprotein cholesterol and accelerated atherosclerosis. Even among this high-risk group, prior studies note considerable variability in risk of coronary artery disease (CAD).
OBJECTIVES
The purpose of this study was to evaluate the cumulative impact of many common DNA variants-as quantified by a polygenic score-on incident CAD among individuals carrying a HeFH variant.
METHODS
We analyzed data from a prospective cohort study of 1,315 individuals who carried a HeFH variant and 1,315 matched family noncarriers derived from a nationwide screening program in the Netherlands, with subsequent replication in 151,009 participants of the UK Biobank.
RESULTS
Despite identification and lipid management within the Dutch screening program, 84 (6.4%) of HeFH variant carriers developed CAD as compared to 45 (3.4%) of matched family members (median follow-up 10.2 years, HR 1.88, 95% CI: 1.31-2.70). Among HeFH variant carriers, a polygenic score was associated with CAD with an effect size similar to low-density lipoprotein cholesterol - HR of 1.35 (95% CI: 1.07-1.70) and 1.41 (95% CI: 1.17-1.70) per standard deviation increase, respectively. When compared to noncarriers, CAD risk increased from 1.24-fold (95% CI: 0.64-2.34) to 3.37-fold (95% CI: 2.11-5.36) across quintiles of the polygenic score. A similar risk gradient, 1.36-fold (95% CI: 0.65-2.85) to 2.88-fold (95% CI: 1.59-5.20), was observed in 429 carriers in the UK Biobank.
CONCLUSIONS
In 2 cohort studies involving 1,744 individuals with genetically confirmed HeFH - the largest study to date - risk of CAD varied according to polygenic background, in some cases approaching the risk observed in noncarriers.
PubMed: 38938725
DOI: 10.1016/j.jacadv.2023.100662 -
JACC. Advances Nov 2023
PubMed: 38938721
DOI: 10.1016/j.jacadv.2023.100664 -
JACC. Advances Nov 2023
PubMed: 38938707
DOI: 10.1016/j.jacadv.2023.100646 -
Frontiers in Toxicology 2024Smoking cigarettes is a cause of serious diseases in smokers, including cardiovascular disease. Through a pathway of endothelial dysfunction, lipid infiltration,...
BACKGROUND
Smoking cigarettes is a cause of serious diseases in smokers, including cardiovascular disease. Through a pathway of endothelial dysfunction, lipid infiltration, macrophage recruitment and vascular remodeling, atherosclerosis is fundamental in the development of most cardiovascular diseases. There is an increasing number of next-generation products (NGP) which provide potentially reduced harm forms of nicotine delivery to adult smokers. This study aimed to optimise an cardiovascular model to assess such products. Human Coronary Artery Endothelial Cells (HCAECs) were cultured on an OrganoPlate2-lane chip (Mimetas BV) combined with THP-1 monocytes under flow conditions.
METHODS
An aqueous aerosol extract from the 1R6F reference cigarette was compared with two categories of NGP, (a heated tobacco product (HTP) and an electronic nicotine delivery system (ENDS)), to assess relative effects on select atherogenic endpoints (oxidative stress, monocyte adhesion, ICAM-1 expression, and inflammatory markers). Following exposure of THP-1 monocytes with the aqueous extracts, the resulting conditioned medium was then added to the HCAEC vessels.
RESULTS
1R6F was consistently the most potent test article, eliciting observed responses at 4x lower concentrations than applied for both the HTP and ENDS. The HTP was more potent than the ENDS product across all endpoints, however, all test articles increased monocyte adhesion. ICAM-1 did not appear to be a main driver for monocyte adhesion, however, this could be due to replicate variability. Upon comparison to an extract-only control exposure, THP-1-medium pre-conditioning was an important mediator of the responses observed.
CONCLUSION
In conclusion, the data suggests that the NGP extracts, containing primary aerosol chemical constituents exhibit a marked reduction in biological activity in the early key events associated with atherogenesis when compared to a cigarette, adding to the weight of evidence for the tobacco harm reduction potential of such products.
PubMed: 38938662
DOI: 10.3389/ftox.2024.1395670 -
JACC. Advances Dec 2023Recent evidence has shown that reproductive factors are associated with an increased risk of heart failure with preserved ejection fraction in women. However, the...
BACKGROUND
Recent evidence has shown that reproductive factors are associated with an increased risk of heart failure with preserved ejection fraction in women. However, the pathogenic pathways underlying this relationship are unclear. Subclinical myocardial fibrosis has been found to be a common pathway in a large proportion of patients with heart failure with preserved ejection fraction.
OBJECTIVES
This study examined the relationship between vital reproductive factors (parity, pregnancy, age at menopause, and use of hormone replacement therapy [HRT]) with interstitial myocardial fibrosis (IMF) and myocardial scar measured by cardiac magnetic resonance imaging (CMR) T1 mapping and late gadolinium enhancement, respectively.
METHODS
There were 596 female participants (mean age 67 ± 8 years) enrolled in MESA (Multi-Ethnic Study of Atherosclerosis) who had complete parity data and underwent CMR. Parity was categorized as 0 live births, 1 to 2, 3 to 4, and ≥5 live births. Multivariable regression models were constructed to assess the associations of parity status, history of null gravidity, age at menopause and HRT with CMR obtained measures of IMF (extracellular volume [ECV], native-T1 time) and myocardial scar.
RESULTS
Women with a history of nulliparity had greater ECV% (β = 0.95 ± 0.28, = 0.001) and native-T1 ms (β = 10.6 ± 4.9, = 0.03) than those who had 1 to 2 live births. These associations were independent of age, traditional cardiovascular risk factors, and interim cardiovascular events. Similar associations were found for women with a history of null gravidity compared to those with a history of pregnancy (ECV% [β = 0.7 ± 0.3, = 0.02] and native-T1 ms [β = 10.6 ± 5.2, = 0.04]). There was no association between age at menopause and HRT with markers of IMF. There were no associations between parity status, null gravidity, and age of menopause with the presence of myocardial scar; however, those who used HRT were independently associated with a lesser risk of myocardial scar (OR: 0.20; 95% CI: 0.05-0.82).
CONCLUSIONS
In a multiethnic cohort, women with a history of nulliparity or null gravidity had greater IMF defined by CMR, while those who used HRT were less likely to have myocardial scar.
PubMed: 38938498
DOI: 10.1016/j.jacadv.2023.100703 -
European Heart Journal. Case Reports Jun 2024The surface of the aorta generally does not show motion unless mobile atheroma, thrombi, vegetations, or intimal flaps are present. We previously described unusual...
BACKGROUND
The surface of the aorta generally does not show motion unless mobile atheroma, thrombi, vegetations, or intimal flaps are present. We previously described unusual mobile filamentous structures in the carotid artery. Here, we describe similar findings in the aorta and their possible cause.
CASE SUMMARY
An 88-year-old female with progressive exertional dyspnoea and severe aortic stenosis had a successful transcatheter aortic valve replacement (TAVR). A filamentous structure was noted on the focused pre-operative 2D transoesophageal echocardiography in the proximal descending aorta and post-TAVR as long strand-like structures attached to the thickened intimal wall with a planar component on 3D imaging. These findings were not associated with symptoms or clinical sequelae on short- and long-term follow-up.
DISCUSSION
The mobile structures that we describe are atypical for atheroma, thrombi, vegetations, and dissections in terms of their form and clinical presentation. 2D imaging showed that the filaments had focal thickening and emerged from the aortic surface. These findings suggest a relationship with the intima, perhaps from atherogenesis or injury with disruption or lifting of the intimal surface. No clinical sequelae were detected that may also relate to their position in the descending aorta and not the arch.
PubMed: 38938470
DOI: 10.1093/ehjcr/ytae263 -
JACC. Advances Oct 2023
PubMed: 38938368
DOI: 10.1016/j.jacadv.2023.100598 -
JACC. Advances Oct 2023
PubMed: 38938348
DOI: 10.1016/j.jacadv.2023.100595 -
Scientific Reports Jun 2024Both hypoxia and the complement lectin pathway (CLP) are involved in atherosclerosis and atherosclerosis-related stroke and acute myocardial infarction (AMI). We have...
Both hypoxia and the complement lectin pathway (CLP) are involved in atherosclerosis and atherosclerosis-related stroke and acute myocardial infarction (AMI). We have previously shown that mannose-binding lectin-associated serine protease-1 (MASP-1), the most abundant enzyme of CLP, induces an inflammatory phenotype of endothelial cells (ECs) by cleaving protease activated receptors (PARs). In the absence of data, we aimed to investigate whether hypoxia and MASP-1 interact at the level of ECs, to better understand their role in atherosclerosis-related diseases. Hypoxia attenuated the wound healing ability of ECs, increased ICAM-1 and decreased ICAM-2 expression and upregulated PAR2 gene expression. Hypoxia and MASP-1 increased GROα and IL-8 production, and endothelial permeability without potentiating each other's effects, whereas they cooperatively disrupted vascular network integrity, activated the Ca, CREB and NFκB signaling pathways, and upregulated the expression of E-selectin, a crucial adhesion molecule in neutrophil homing. VCAM-1 expression was not influenced either by hypoxia, or by MASP-1. In summary, hypoxia potentiates the effect of MASP-1 on ECs, at least partially by increasing PAR expression, resulting in interaction at several levels, which may altogether exacerbate stroke and AMI progression. Our findings suggest that MASP-1 is a potential drug target in the acute phase of atherosclerosis-related diseases.
Topics: Humans; Mannose-Binding Protein-Associated Serine Proteases; Atherosclerosis; Endothelial Cells; Signal Transduction; Cell Hypoxia; NF-kappa B; Receptor, PAR-2; Human Umbilical Vein Endothelial Cells; Intercellular Adhesion Molecule-1; E-Selectin; Interleukin-8
PubMed: 38937560
DOI: 10.1038/s41598-024-64479-6