-
Biochimica Et Biophysica Acta.... Jun 2024The prevalence of cardiovascular diseases (CVDs) is increasing in the last decades, even is the main cause of death in first world countries being atherosclerosis one of...
Potential protective role of let-7d-5p in atherosclerosis progression reducing the inflammatory pathway regulated by NF-κB and vascular smooth muscle cells proliferation.
The prevalence of cardiovascular diseases (CVDs) is increasing in the last decades, even is the main cause of death in first world countries being atherosclerosis one of the principal triggers. Therefore, there is an urgent need to decipher the underlying mechanisms involved in atherosclerosis progression. In this respect, microRNAs dysregulation is frequently involved in the progression of multiple diseases including CVDs. Our aim was to demonstrate that let-7d-5p unbalance could contribute to the pathophysiology of atherosclerosis and serve as a potential diagnostic biomarker. We evaluated let-7d-5p levels in vascular biopsies and exosome-enriched extracellular vesicles (EVs) from patients with carotid atherosclerosis and healthy donors. Moreover, we overexpressed let-7d-5p in vitro in vascular smooth muscle cells (VSMCs) to decipher the targets and the underlying mechanisms regulated by let-7d-5p in atherosclerosis. Our results demonstrate that let-7d-5p was significantly upregulated in carotid plaques from overweight patients with carotid atherosclerosis. Moreover, in EVs isolated from plasma, we found that let-7d-5p levels were increased in carotid atherosclerosis patients compared to control subjects specially in overweight patients. Receiver Operating Characteristic (ROC) analyses confirmed its utility as a diagnostic biomarker for atherosclerosis. In VSMCs, we demonstrated that increased let-7d-5p levels impairs cell proliferation and could serve as a protective mechanism against inflammation by impairing NF-κB pathway without affecting insulin resistance. In summary, our results highlight the role of let-7d-5p as a potential therapeutic target for atherosclerosis since its overexpression induce a decrease in inflammation and VSMCs proliferation, and also, as a novel non-invasive diagnostic biomarker for atherosclerosis in overweight patients.
PubMed: 38945455
DOI: 10.1016/j.bbadis.2024.167327 -
Atherosclerosis Jun 2024Atherosclerosis manifests itself differently in men and women with respect to plaque initiation, progression and plaque composition. The observed delay in plaque... (Review)
Review
Atherosclerosis manifests itself differently in men and women with respect to plaque initiation, progression and plaque composition. The observed delay in plaque progression in women is thought to be related to the hormonal status of women. Also features associated with the vulnerability of plaques to rupture seem to be less frequently present in women compared to men. Current invasive and non-invasive imaging modalities allow for visualization of plaque size, composition and high risk vulnerable plaque features. Moreover, image based modeling gives access to local shear stress and shear stress-related plaque growth. In this review, current knowledge on sex-related differences in plaque size, composition, high risk plaque features and shear stress related plaque growth in carotid and coronary arteries obtained from imaging are summarized.
PubMed: 38944895
DOI: 10.1016/j.atherosclerosis.2024.117616 -
Atherosclerosis Jun 2024The role of aortic mineralization in the pathogenesis of acute type B aortic dissection (TBAD) is unclear. Whether thoracic aortic calcification (TAC) and circulating...
BACKGROUND AND AIMS
The role of aortic mineralization in the pathogenesis of acute type B aortic dissection (TBAD) is unclear. Whether thoracic aortic calcification (TAC) and circulating alkaline phosphatase (ALP) activity are associated with acute TBAD risk remains elusive.
METHODS
Observational and Mendelian randomization (MR) studies were conducted sequentially. Using propensity score matching (1:1) by age and sex, patients with acute TBAD (n = 125) were compared with control patients (n = 125). Qualitative (score) and quantitative (volume) analyses of the TAC burden on different thoracic aortic segments were conducted using non-enhanced computed tomography. Univariate and multivariate analyses were used to identify significant independent risk factors for TBAD and TAC burden, respectively. MR was finally used to determine the causal relationship between elevated ALP activity and TBAD risk.
RESULTS
The qualitative and quantitative analyses revealed that TAC burden was significantly higher in the TBAD group, except for in the ascending aortic segment (both p < 0.05). Preoperative circulating ALP was significantly elevated in the TBAD group (p < 0.001). The elevated TAC burden score on the descending thoracic aortic segment (odds ratio [OR] 3.31, 95% confidence interval [CI] 1.31-8.37) and increased ALP activity (OR 1.03, 95% CI 1.01-1.06) was independently associated with TBAD risk. Interestingly, ALP was significantly positively associated with TAC burden, and MR analyses confirmed that ALP genetically predicted TBAD risk.
CONCLUSIONS
Elevated ALP may trigger TBAD risk via the increased volume of TAC. Aortic mineralization may not protect the aorta itself.
PubMed: 38944894
DOI: 10.1016/j.atherosclerosis.2024.118519 -
Aging Jun 2024Cathepsin L (CTSL) has been implicated in aging and age-related diseases, such as cardiovascular diseases, specifically atherosclerosis. However, the underlying...
Cathepsin L (CTSL) has been implicated in aging and age-related diseases, such as cardiovascular diseases, specifically atherosclerosis. However, the underlying mechanism(s) is not well documented. Recently, we demonstrated a role of CUT-like homeobox 1 (CUX1) in regulating the p16-dependent cellular senescence in human endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) via its binding to an atherosclerosis-associated functional SNP (fSNP) rs1537371 on the locus. In this study, to determine if CTSL, which was reported to proteolytically activate CUX1, regulates cellular senescence via CUX1, we measured the expression of CTSL, together with CUX1 and p16, in human ECs and VSMCs undergoing senescence. We discovered that CUX1 is not a substrate that is cleaved by CTSL. Instead, CTSL is an upstream regulator that activates transcription indirectly in a process that requires the proteolytic activity of CTSL. Our findings suggest that there is a transcription factor in between CTSL and CUX1, and cleavage of this factor by CTSL can activate CUX1 transcription, inducing endothelial senescence. Thus, our findings provide new insights into the signal transduction pathway that leads to atherosclerosis-associated cellular senescence.
PubMed: 38944813
DOI: 10.18632/aging.205955 -
Mymensingh Medical Journal : MMJ Jul 2024Parkinson's disease (PD) is a chronic, progressive neurodegenerative disease with unknown etiology. Some previous studies suggest that elevated serum homocysteine level...
Parkinson's disease (PD) is a chronic, progressive neurodegenerative disease with unknown etiology. Some previous studies suggest that elevated serum homocysteine level is a risk factor for stroke, ischemic heart disease; atherosclerosis and neurodegenerative diseases like Parkinson's disease. Serum homocysteine level relates with Parkinson's disease through various mechanisms including gene defect, apoptosis, oxidative stress and DNA damage. Some recent studies reveal that serum homocysteine level is elevated in Parkinson's disease patient compared to healthy individuals. This study was aimed to compare the serum homocysteine level in Parkinson's disease patients and age and sex matched apparently healthy individuals. This was a case control study which was conducted in Department of Neurology and Medicine, Mymensingh Medical College Hospital, Mymensingh during November 2019 to April 2021. Total 55 cases of Parkinson's disease patients and age and sex matched 55 apparently healthy controls were enrolled in this study. Demographics and clinical data were collected using structured case record form and adopting purposive type of sampling method. Serum homocysteine level was measured in both case and control groups. The study reveals that, average age of the patients and control group was in sixth decade. Male predominance was found with male to female ratio was 1.5:1 in case group. Both groups showed almost similar demographic profiles. Twenty-nine (52.72%) patients of Parkinson's disease observed higher serum homocysteine level in contrast to only 8(14.54%) in control group. The mean serum homocysteine ±SD was 15.43±6.04μmol/L in case group and 10.04±5.31μmol/L in control group; the difference was statistically significant (p=0.001). Mean serum homocysteine levels were measured progressively higher with increased duration and advanced stages of disease. It was concluded that, serum homocysteine level is higher in Parkinson's disease patients than normal healthy individuals. In addition, there was significant positive correlation of elevated serum homocysteine with increased duration of Parkinson's disease and advanced stages of the disease.
Topics: Humans; Homocysteine; Parkinson Disease; Male; Female; Case-Control Studies; Middle Aged; Aged; Adult; Risk Factors
PubMed: 38944701
DOI: No ID Found -
Atherosclerosis Jun 2024
PubMed: 38944546
DOI: 10.1016/j.atherosclerosis.2024.118522 -
Atherosclerosis Jun 2024Patients with myocardial ischemia without obstructive coronary artery disease often have coronary microvascular dysfunction (CMD) and associated increased risk of...
BACKGROUND
Patients with myocardial ischemia without obstructive coronary artery disease often have coronary microvascular dysfunction (CMD) and associated increased risk of cardiovascular (CV) events and anginal hospitalizations. Epicardial adipose tissue (EAT) covers much of the myocardium and coronary arteries and when dysfunctional, secretes proinflammatory cytokines and is associated with CV events. While oxidative stress and systemic inflammation are associated with CMD, the relationship between EAT and CMD in women is not well known.
METHODS
Women diagnosed with CMD (n = 21) who underwent coronary computed tomography with coronary artery calcium (CAC) scoring were compared to a reference group (RG) of women referred for CAC screening for preventive risk assessment (n = 181). EAT attenuation (Hounsfield units (HU)) was measured adjacent to the proximal right coronary artery, along with subcutaneous adipose tissue (SCAT). Two-sample t-tests with unequal variances were utilized.
RESULTS
Mean age of the CMD group was 56 ± 8 years and body mass index (BMI) was 31.6 ± 6.8 kg/m. CV risk factors in the CMD group were prevalent: 67 % hypertension, 44 % hyperlipidemia, and 33 % diabetes. Both CMD and RG had similar CAC score (25.86 ± 59.54 vs. 24.17 ± 104.6; p = 0.21. In the CMD group, 67 % had a CAC of 0. Minimal atherosclerosis (CAD-RADS 1) was present in 76 % of women with CMD. The CMD group had lower EAT attenuation than RG (-103.3 ± 6.33 HU vs. -97.9 ± 8.3 HU, p = 0.009, respectively). There were no differences in SCAT attenuation. Hypertension, smoking history, age, BMI, and CAC score did not correlate with EAT in either of the groups.
CONCLUSIONS
Women with CMD have decreased EAT attenuation compared to RG women. EAT-mediated inflammation and changes in vascular tone may be a mechanistic contributor to abnormal microvascular reactivity. Clinical trials testing therapeutic strategies to decrease EAT may be warranted in the management of CMD.
PubMed: 38944545
DOI: 10.1016/j.atherosclerosis.2024.118520 -
Thrombosis Research Jun 2024
PubMed: 38944019
DOI: 10.1016/j.thromres.2024.109069 -
Reproductive Biomedicine Online May 2024The pathophysiology of endometriosis remains unclear. Retrograde menstruation could be a phenomenon that initiates the process, but it may not explain the entire...
The pathophysiology of endometriosis remains unclear. Retrograde menstruation could be a phenomenon that initiates the process, but it may not explain the entire pathophysiology of endometriosis. Current evidence suggests that endometriosis is a type of chronic inflammatory disease. Many conditions that affect the vascular endothelium, including atherosclerosis, cardiovascular disease and pre-eclampsia, have been shown to be associated with endometriosis. Evidence to date suggests a complex interaction in endometriosis between angiogenesis, hormones and immunological changes stemming from chronic inflammation, with the inflammatory cells releasing cytokines and chemokines including tumour necrosis factor-α (TNF-α). Indeed, TNF-α is considered to be one of the possible markers of endometriosis in the blood, endometrium or menstrual blood. We emphasize the importance of pursuing research for novel and safer anti-inflammatory and immunomodulatory drugs that can be used by patients with endometriosis on a long-term basis.
PubMed: 38943810
DOI: 10.1016/j.rbmo.2024.104292 -
BMC Public Health Jun 2024The metabolic score for visceral fat (METS-VF) quantifies the cumulative burden of visceral and intra-abdominal adipose tissues. However, the relationship between the...
BACKGROUND
The metabolic score for visceral fat (METS-VF) quantifies the cumulative burden of visceral and intra-abdominal adipose tissues. However, the relationship between the METS-VF and carotid atherosclerosis (CAS) has not been extensively explored. Therefore, this study aimed to investigate the association between the METS-VF and CAS.
METHODS
This cross-sectional study enrolled 7089 Chinese adults who underwent physical examinations at the Zhenhai Lianhua Hospital, Zhejiang, China, in 2020. Multivariable logistic regression analysis was used to explore the linear relationship between METS-VF and CAS. Generalised additive models (GAM) were employed to evaluate potential nonlinear associations. The inflection points of METS-VF were determined using segmented logistic regression analysis optimised for maximum likelihood ratios and recursive algorithms.
RESULTS
Multivariable logistic regression analysis revealed a positive correlation between METS-VF and CAS (odds ratio [OR]: 1.824, 95% confidence interval [CI]: 1.753-1.899; P < 0.001). The GAM analysis confirmed a nonlinear association between them [effective degrees of freedom: 4.803, χ: 876.7, P < 0.001], with an inflection point at a METS-VF of 8.09 (P < 0.001 for log-likelihood ratio test). Below this inflection point, METS-VF exhibited a significant positive association with CAS risk (OR: 1.874, 95% CI: 1.796-1.954; P < 0.001). Conversely, no significant association was observed when METS-VF ≥ 8.09 (OR: 0.998, 95% CI: 0.786-1.268; P = 0.989).
CONCLUSIONS
METS-VF and CAS demonstrated a positive non-linear correlation, with the curve indicating a saturation effect at METS-VF = 8.09.
Topics: Humans; Cross-Sectional Studies; Male; Female; Intra-Abdominal Fat; Middle Aged; China; Carotid Artery Diseases; Adult; Metabolic Syndrome; Aged; Risk Factors; Logistic Models
PubMed: 38943105
DOI: 10.1186/s12889-024-19186-2