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Journal of Clinical Lipidology May 2024Coronary microvascular dysfunction (CMD) is a common occurrence in individuals with insulin resistance (IR). Homeostatic model assessment for insulin resistance...
BACKGROUND
Coronary microvascular dysfunction (CMD) is a common occurrence in individuals with insulin resistance (IR). Homeostatic model assessment for insulin resistance (HOMA-IR) is a widely used surrogate marker of IR, although recent studies suggest Triglyceride-Glucose (TyG) index is a superior marker of IR that had a better accuracy to predict Type 2 Diabetes or cardiovascular outcomes than HOMA-IR.
OBJECTIVES
We aimed to assess the accuracy and usefulness of TyG index and HOMA-IR for predicting CMD as assessed with echocardiographic coronary flow reserve (CFR) measurement.
METHODS
All cases included in the institutional CFR registry were retrospectively reviewed, and 656 cases without epicardial coronary artery disease and without major risk factors for atherosclerosis were included. A CFR ≤2.0 was defined as CMD.
RESULTS
TyG index was available in all cases, while HOMA-IR was available in 398 cases. Both TyG index and HOMA-IR were associated with CMD on univariate analyses, while after adjustment for potential confounders HOMA-IR (OR:1.38, 95 %CI:1.14-1.67, p = 0.001) but not TyG index(OR:1.48, 95 %CI:0.82-2.67, p = 0.19) was associated with CMD. The predictive accuracy of HOMA-IR (c-statistic:0.63, 95 %CI:0.54-0.72, p = 0.003) was higher than TyG index(c-statistic:0.55, 95 %CI:0.47-0.63, p = 0.13), although the difference was not statistically significant (DeLong p = 0.23). There was strong evidence favoring a true difference between CMD vs. non-CMD groups for HOMA-IR (BF:3507) but not for TyG index(BF:0.66).
CONCLUSIONS
HOMA-IR, but not TyG index, is closely associated with CMD.
PubMed: 38955587
DOI: 10.1016/j.jacl.2024.04.135 -
Phytomedicine : International Journal... Jun 2024Atherosclerosis (AS) is the main pathological basis for the development of cardiovascular diseases. Vascular inflammation is an important factor in the formation of AS,...
BACKGROUND
Atherosclerosis (AS) is the main pathological basis for the development of cardiovascular diseases. Vascular inflammation is an important factor in the formation of AS, and macrophage pyroptosis plays a key role in AS due to its unique inflammatory response. Guizhitongluo Tablet (GZTLT) has shown clinically effective in treating patients with AS, but its mechanism is elusive.
PURPOSE
This study was to determine the effects of GZTLT on atherosclerotic vascular inflammation and pyroptosis and to understand its underlying mechanism.
MATERIALS AND METHODS
The active constituents of GZTLT were analysed by means of UPLC-HRMS. In vivo experiments were performed using ApoE mice fed a high fat diet for 8 weeks, followed by treatment with varying concentrations of GZTLT orally by gavage and GsMTx4 (GS) intraperitoneally and followed for another 8 weeks. Oil red O, Haematoxylin-eosin (HE) and Masson staining were employed to examine the lipid content, plaque size, and collagen fibre content of the mouse aorta. Immunofluorescence staining was utilised to identify macrophage infiltration, as well as the expression of Piezo1 and NLRP3 proteins in aortic plaques. The levels of aortic inflammatory factors were determined using RT-PCR and ELISA. In vitro, foam cell formation in bone marrow-derived macrophages (BMDMs) was observed using Oil Red O staining. Intracellular Ca measurements were performed to detect the calcium influx in BMDMs, and the expression of NLRP3 and its related proteins were detected by Western blot.
RESULTS
The UPLC-HRMS analysis revealed 31 major components of GZTLT. Our data showed that GZTLT inhibited aortic plaque formation in mice and increased plaque collagen fibre content to stabilise plaques. In addition, GZTLT could restrain the expression of serum lipid levels and suppress macrophage foam cell formation. Further studies found that GZTLT inhibited macrophage infiltration in aortic plaques and suppressed the expression of inflammatory factors. It is noteworthy that GZTLT can restrain Piezo1 expression and reduce Ca influx in BMDMs. Additionally, we found that GZTLT could regulate NLRP3 activation and pyroptosis by inhibiting Piezo1.
CONCLUSION
The present study suggests that GZTLT inhibits vascular inflammation and macrophage pyroptosis through the Piezo1/NLRP3 signaling pathway, thereby delaying AS development. Our finding provides a potential target for AS treatment and drug discovery.
PubMed: 38955059
DOI: 10.1016/j.phymed.2024.155827 -
Atherosclerosis Apr 2024The immuno-inflammatory response is a crucial early step in the development of acute coronary syndrome (ACS). In this study, we investigated whether immunoglobulin M...
BACKGROUND AND AIMS
The immuno-inflammatory response is a crucial early step in the development of acute coronary syndrome (ACS). In this study, we investigated whether immunoglobulin M (IgM) in the body's initial immune response can predict the prognosis of patients with ACS.
METHODS
This prospective cohort study enrolled 1556 ACS patients at Beijing Hospital between March 2017 and October 2020. All patients underwent coronary angiography (CAG). The serum IgM concentration and biochemical indicators were evaluated prior to CAG. The primary endpoint was the composite endpoint of major adverse cardiovascular and cerebrovascular events (MACCEs). Multivariate Cox proportional hazards models was used to explore the association between IgM levels and the endpoint.
RESULTS
The average serum IgM levels of the population was 61.3 (42.6-88.4) mg/dL. During the median follow-up period of 55 months, 150 MACCEs occurred. Kaplan-Meier analysis showed that low serum IgM levels were associated with occurrence of MACCEs (log-rank p = 0.009). Univariate Cox proportional hazards models showed that low serum IgM (≤78.05 mg/dL) was associated with MACCEs (hazard ratio (HR) 1.648, 95 % confidence interval (CI): 1.129-2.406, p = 0.010). In patients with IgM ≤78.05 mg/dL, the HR for partially adjusted MACCEs events was 1.576 (95 % CI: 1.075-2.310) and 1.930 (95 % CI: 1.080-3.449) after adjusting for multiple covariates. The subgroup analysis showed that for patients in ≤24 BMI, never smoking and non-dyslipidemia subgroup, the lower serum IgM levels was significantly associated with the risk of MACCEs (p < 0.001, p = 0.037, p = 0.024, respectively).
CONCLUSIONS
Low serum IgM levels was independently associated with MACCEs in ACS patients, especially for patients without obesity, smoking and dyslipidemia.
PubMed: 38954858
DOI: 10.1016/j.atherosclerosis.2024.117552 -
Herz Jul 2024Cardiovascular diseases are the leading cause of death worldwide. Pathophysiologically, metabolic and inflammatory processes contribute substantially to the development... (Review)
Review
Cardiovascular diseases are the leading cause of death worldwide. Pathophysiologically, metabolic and inflammatory processes contribute substantially to the development and progression of cardiovascular diseases. Over the past decade, the role of disease-propagating inflammatory processes has been strengthened and reframed, leading to trials testing anti-inflammatory drugs for the treatment of atherosclerosis and its complications. Despite these achievements, further research in both pre-clinical and clinical studies is warranted to explore new targets, to better identify responders, and to refine therapy strategies to combat inflammation in human disease. Environmental disturbances, so-called lifestyle-associated cardiovascular risk factors, greatly alter the immune system in general and leukocytes in particular, thus affecting the progression of atherosclerosis. Epidemiological studies have shown that exposure to mental stress can be closely linked to the occurrence of cardiovascular disease. Here, we describe how acute and chronic mental stress alter the immune system via neuroimmune interactions, thereby modifying vascular inflammation. In addition, we identify gaps that still need to be addressed in the future.
PubMed: 38954012
DOI: 10.1007/s00059-024-05254-1 -
European Heart Journal. Cardiovascular... Jul 2024There is increasing evidence that plaque instability in the extracranial carotid artery may lead to an increased stroke risk independently of the degree of stenosis. We...
AIMS
There is increasing evidence that plaque instability in the extracranial carotid artery may lead to an increased stroke risk independently of the degree of stenosis. We aimed to determine diagnostic accuracy of vulnerable and stable plaque using noninvasive imaging modalities when compared to histology in patients with symptomatic and asymptomatic carotid atherosclerosis.
METHODS AND RESULTS
Medline Ovid, Embase, Cochrane Library, and Web of Science were searched for diagnostic accuracy of noninvasive imaging modalities (CT, MRI, US) in the detection of 1) vulnerable/stable plaque, and 2) vulnerable/stable plaque characteristics, compared to histology. The quality of included studies was assessed by QUADAS-2 and univariate and bivariate random-effect meta-analyses were performed. We included 36 vulnerable and 5 stable plaque studies in the meta-analysis, and out of 211 plaque characteristics from remaining studies, we classified 169 as vulnerable and 42 as stable characteristics (28 CT, 120 MRI, 104 US characteristics). We found that MRI had high accuracy [90% (95% CI: 82-95%)] in the detection of vulnerable plaque, similar to CT [86% (95% CI: 76-92%); P > 0.05], whereas US showed less accuracy [80% (95% CI: 75-84%); P = 0.013]. CT showed high diagnostic accuracy in visualizing characteristics of vulnerable or stable plaques (89% and 90%) similar to MRI (86% and 89%; P > 0.05); however, US had lower accuracy (77%, P < 0.001 and 82%, P > 0.05).
CONCLUSION
CT and MRI have a similar, high performance in detecting vulnerable carotid plaques, whereas US showed significantly less diagnostic accuracy. Moreover, MRI visualized all vulnerable plaque characteristics allowing for a better stroke risk assessment.
REGISTRATION
PROSPERO ID CRD42022329690.
PubMed: 38953552
DOI: 10.1093/ehjci/jeae144 -
Minerva Surgery Jul 2024
PubMed: 38953417
DOI: 10.23736/S2724-5691.24.10199-2 -
Frontiers in Cardiovascular Medicine 2024In recent years, the role of macrophages as the primary cell type contributing to foam cell formation and atheroma plaque development has been widely acknowledged.... (Review)
Review
In recent years, the role of macrophages as the primary cell type contributing to foam cell formation and atheroma plaque development has been widely acknowledged. However, it has been long recognized that diffuse intimal thickening (DIM), which precedes the formation of early fatty streaks in humans, primarily consists of lipid-loaded smooth muscle cells (SMCs) and their secreted proteoglycans. Recent studies have further supported the notion that SMCs constitute the majority of foam cells in advanced atherosclerotic plaques. Given that SMCs are a major component of the vascular wall, they serve as a significant source of microvesicles and exosomes, which have the potential to regulate the physiology of other vascular cells. Notably, more than half of the foam cells present in atherosclerotic lesions are of SMC origin. In this review, we describe several mechanisms underlying the formation of intimal foam-like cells in atherosclerotic plaques. Based on these mechanisms, we discuss novel therapeutic approaches that have been developed to regulate the generation of intimal foam-like cells. These innovative strategies hold promise for improving the management of atherosclerosis in the near future.
PubMed: 38952543
DOI: 10.3389/fcvm.2024.1381520 -
Frontiers in Cardiovascular Medicine 2024While Traditional Chinese Medicine (TCM) boasts an extensive historical lineage and abundant clinical expertise in addressing atherosclerosis, this field is yet to be...
BACKGROUND
While Traditional Chinese Medicine (TCM) boasts an extensive historical lineage and abundant clinical expertise in addressing atherosclerosis, this field is yet to be penetrated adequately by bibliometric studies. This study is envisaged to evaluate the contemporary scenario of TCM in conjunction with atherosclerosis over the preceding decade while also identifying forthcoming research trends and emerging topics via the lens of bibliometric analysis.
METHODS
Literature pertaining to TCM and atherosclerosis, circulated between January 1, 2012 and November 14, 2023, was garnered for the purpose of this research. The examination embraced annual publications, primary countries/regions, engaged institutions and authors, scholarly journals, references, and keywords, utilizing analytical tools like Bibliometrix, CiteSpace, ScimagoGraphica, and VOSviewer present in the R package.
RESULT
This field boasts a total of 1,623 scholarly articles, the majority of which have been contributed by China in this field, with significant contributions stemming from the China Academy of Traditional Chinese Medicine and the Beijing University of Traditional Chinese Medicine. Moreover, this field has received financial support from both the National Natural Science Foundation of China and the National Key Basic Research Development Program. Wang Yong tops the list in terms of publication count, while Xu Hao's articles take the lead for the total number of citations, positioning them at the core of the authors' collaborative network. The Journal of Ethnopharmacology leads with the most publications and boasts the greatest total number of citations. Principal research foci within the intersection of Chinese Medicine and Atherosclerosis encompass disease characteristics and pathogenic mechanisms, theoretical underpinnings and syndrome-specific treatments in Chinese medicine, potentialities of herbal interventions, and modulation exerted by Chinese medicines on gut microbiota.
CONCLUSION
This analysis offers a sweeping survey of the contemporary condition, principal foci, and progressive trends in worldwide research related to Traditional Chinese Medicine (TCM) and atherosclerosis. It further delves into an in-depth dissection of prominent countries, research institutions, and scholars that have made noteworthy strides in this discipline. Additionally, the report analyzes the most cited articles, research developments, and hotspots in the field, providing a reference for future research directions for clinical researchers and practitioners.
PubMed: 38952541
DOI: 10.3389/fcvm.2024.1400130 -
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi =... Jun 2024Objective To explore a simple and feasible method for whole-mount immunofluorescence staining of lymphatic vessels in the ApoE mouse model of atherosclerosis. Methods...
Objective To explore a simple and feasible method for whole-mount immunofluorescence staining of lymphatic vessels in the ApoE mouse model of atherosclerosis. Methods Aortic specimens were carefully excised from the ApoE mouse model. Following immunostaining with specific antibodies against smooth muscle actin (SMA) and lymphatic vessel endothelial receptor 1 (LYVE1), the aortas, including the aortic root, were subjected to a 30-minute treatment with 5 g/L Sudan Black B solution. This step was instrumental in minimizing the autofluorescent background of the tissue. Thereafter, the aortas were processed through a clearing protocol and imaged within a purpose-built chamber under a fluorescence microscope. Results The pretreatment with 5 g/L Sudan Black B effectively suppressed the autofluorescent signals emanating from the vascular structures, thereby enhancing the contrast and clarity of the specific fluorescence signals associated with the lymphatic vessels. This enhancement in signal quality did not compromise the integrity or specificity of the immunofluorescent markers. Conclusion A facile, highly specific, and effective approach for the visualization of lymphatic vessels in whole-mount aortic preparations from ApoE mice is established.
Topics: Animals; Lymphatic Vessels; Mice; Aorta; Apolipoproteins E; Fluorescent Antibody Technique; Adventitia; Atherosclerosis; Male; Mice, Inbred C57BL; Mice, Knockout; Staining and Labeling; Microscopy, Fluorescence
PubMed: 38952092
DOI: No ID Found -
Annals of Clinical and Translational... Jul 2024To examine the associations of renin-angiotensin system (RAS) inhibitor use with postmortem brain insulin signaling and neuropathology.
OBJECTIVE
To examine the associations of renin-angiotensin system (RAS) inhibitor use with postmortem brain insulin signaling and neuropathology.
METHODS
Among Religious Orders Study participants, 150 deceased and autopsied older individuals (75 with diabetes matched to 75 without by age at death, sex, and education) had measurements of insulin receptor substrate-1 (IRS-1) and RAC-alpha serine/threonine protein kinase (AKT1) collected in the prefrontal cortex using ELISA and immunohistochemistry. Alzheimer's disease (AD), brain infarcts, and cerebral vessel pathology data were assessed by systematic neuropathologic evaluations. RAS inhibitor use was determined based on visual inspection of medication containers during study visits. The associations of RAS inhibitor use with brain insulin signaling measures and neuropathology were examined using adjusted regression analyses.
RESULTS
Of the 90 RAS inhibitor users (54 with diabetes), 65 had used only angiotensin-converting enzyme inhibitors, 11 only angiotensin II receptor blockers, and 14 used both. RAS inhibitor use was associated with lower pTAKT1/total AKT1, but not with pSIRS-1/total IRS-1 or the density of cells stained positive for pS IRS-1. RAS inhibitor use was not associated with the level of global AD pathology or amyloid beta burden, but it was associated with a lower tau-neurofibrillary tangle density. Additionally, we found a significant interaction between diabetes and RAS inhibitors on tangle density. Furthermore, AKT1 phosphorylation partially mediated the association of RAS inhibitor use with tau tangle density. Lastly, RAS inhibitor use was associated with more atherosclerosis, but not with other cerebral blood vessel pathologies or cerebral infarcts.
INTERPRETATION
Late-life RAS inhibitor use may be associated with lower brain AKT1 phosphorylation and fewer neurofibrillary tangles.
PubMed: 38952081
DOI: 10.1002/acn3.52132