Search Results (67)

Background and Objectives: Accurate evaluation of vulnerable carotid atherosclerotic plaques remains essential for preventing ischemic stroke. Conventional imaging modalities such as ultrasound and computed tomography angiography (CTA) have limited capacity to identify histopathological features of plaque instability, including fibrous cap rupture, lipid-rich necrotic core, and intraplaque hemorrhage. Artificial intelligence (AI) techniques—particularly deep learning (DL) and radiomics—have recently emerged as valuable adjuncts to standard imaging, achieving AUC values of 0.83–0.99 across modalities in identifying vulnerable plaques. This scoping review summarizes the available evidence on the application of AI in the detection and assessment of vulnerable carotid plaques. Methods: A systematic search of the English-language literature was conducted in MEDLINE, SCOPUS, and CENTRAL from 2000 to 30 June 2025, following the PRISMA-ScR framework. Eligible studies applied AI-based approaches (machine learning, deep learning, or radiomics) to evaluate carotid plaque vulnerability using ultrasound, CTA, or MRI. Extracted outcomes included diagnostic performance, correlation with histopathology or neurological events, and predictive modeling for stroke risk. Results: Of 201 records screened, 12 studies met inclusion criteria (ultrasound = 6; CTA = 4; high-resolution MRI = 2; publication years 2021–2025). All reported receiver operating characteristic area-under-the-curve (ROC-AUC) values for endpoints related to plaque vulnerability (symptomatic versus asymptomatic status, presence of intraplaque hemorrhage or lipid-rich necrotic core, fibrous-cap surrogates, and, less frequently, short-term cerebrovascular events). For ultrasound, contrast-enhanced videomics achieved an AUC of 0.87 (10 centers; n = 205), B-mode texture/radiomics reached 0.87 (n = 150), and segmentation-assisted models 0.827 (n = 202); other ultrasound models reported AUCs of 0.88–0.91. For CTA, a symptomatic-plaque machine-learning model yielded AUC 0.89 ( n = 106); a perivascular-adipose-tissue (PVAT) radiomics nomogram achieved AUC 0.836 on external validation; a histology-referenced pilot attained AUC 0.987; and one mild-stenosis TIA model reported ROC performance. For high-resolution MRI (HR-MRI), radiomics-based models showed AUC 0.835–0.864 in single-modality cohorts and up to 0.984 with multi-contrast inputs. Across modalities, AUC ranges were: ultrasound 0.827–0.91, CTA 0.836–0.987 (external 0.836), and HR-MRI 0.835–0.984. Only two out of twelve studies performed external validation; calibration and decision-curve analyses were rarely provided, and most cohorts were single-center, limiting generalizability. Conclusions: AI demonstrates strong potential as a complementary tool for evaluating carotid plaque vulnerability, with high diagnostic performance across imaging modalities. Reported AUCs ranged from 0.83 to 0.99 based primarily on internal or hold-out validation, representing the upper bound of theoretical rather than real-world performance. Nonetheless, large prospective multicenter studies with standardized protocols, histopathological correlation, and external validation are required before clinical integration into stroke prevention pathways. Full article

Background/Objectives: The causes and mechanisms underlying the development of leptin resistance (LR) in patients with cardiovascular disease (CVD) remain unknown. Investigating the characteristics of adipose tissue in patients with CVD is a relevant scientific problem that may help to uncover the missing links in the pathogenesis of LR. This study aimed to evaluate systemic and local markers of LR in patients with different forms of CVD, and to determine the prevalence and tissue-specific expression patterns that contribute to LR. Methods: The study included 108 patients with myocardial infarction (MI), 96 patients with chronic coronary heart disease (CHD), and 96 patients with acquired heart disease (AHD). On day 1 of admission to the hospital, leptin and leptin receptor concentrations and the serum-free leptin index (FLI) were measured. Leptin resistance (LR) was defined as a leptin level of >6.45 ng/mL and FLI of >25. In chronic CHD and AHD patients, LEP, LEPR1, LEPR2, LEPR2/2, LEPR3, LEPR3/2, and LEPR4 expression as well as leptin and soluble leptin receptor secretion were assessed in subcutaneous (SAT), epicardial (EAT), and perivascular (PVAT) adipose tissue. Results: MI and chronic CHD patients are characterized by elevated leptin levels and high FLI values in the blood serum, which indicates a high prevalence of LR, in contrast to AHD patients. In chronic CHD, the LR level was highest in EAT and moderate in SAT. Reduced leptin sensitivity in EAT is underlied by decreased expression of LEPR1, LEPR2, LEPR2/2, LEPR3, LEPR3/2, and LEPR4, and increased leptin production by epicardial adipocytes, which contributes to enhancement of leptin resistance at the systemic level. Conclusions: A high LR rate was detected in patients with MI and chronic CHD. The identified changes in EAT lead to the development of leptin resistance in chronic CHD patients. Full article

Perivascular adipose tissue (PVAT) is a unique fat depot that is distributed around blood vessels, contiguous with the vascular adventitia. Due to this proximity, it serves as a local source of adipokines and vasoregulatory factors. Similar to other adipose depots, PVAT is responsive to changes in metabolic state and, at least in mice, can transition to a thermogenic adipocyte phenotype depending on metabolic health. Cardiovascular disease risk is highly correlated with metabolic health and increases substantially in individuals with obesity or metabolic syndrome. Cardiovascular diseases, including atherosclerosis/coronary artery disease, aortic aneurysm, hypertension, arterial stiffening, and heart failure, have been associated with PVAT dysregulation. Understanding the cardiovascular protective effects of healthy PVAT can provide ways to modify disease progression to re-establish functional homeostasis. This review focuses on experimental studies that specifically define a signaling axis between PVAT and the cardiovascular system that provide cardioprotection. Our focus is primarily on the secreted contents of extracellular vesicles that initiate this adipose signaling axis and regulation of extracellular vesicle release by the trafficking molecule, RAB27a. We review the current literature on human and mouse studies and major categories of PVAT-derived signaling components including microRNAs, lipids, and proteins that contribute to cardiovascular homeostasis. Full article

This study examined the expression of the renin-angiotensin system (RAS) and inflammatory markers in cardiovascular complications associated with long-term type 1 diabetes (T1D) using a rat model. After 24 weeks of streptozotocin-induced T1D, the animals exhibited metabolic alterations indicative of both cardiac and renal dysfunction. Tissue-specific dysregulation of RAS components and pro-inflammatory markers were observed in the heart, aorta, and perivascular adipose tissue (PVAT). In the heart, there was a significant upregulation of both classical (AT1R, 1.00 (0.22) vs. 1.70 (0.45) R.U.) and counter-regulatory RAS components (ACE2, 1.00 (0.43) vs. 1.96 (0.67) R.U.; p < 0.001) and MasR (1.00 (0.56) vs. 1.33 (0.29) R.U.; p = 0.004). The aorta displayed increased expression of classical RAS components alongside a significant reduction in ACE2 expression (1.00 (0.74) vs. 0.51 (0.48) R.U.; p < 0.032). Notably, PVAT showed a significant overexpression of classical RAS components (ACE 1.00 (0.22) vs. 4.08 (1.32) R.U.; p < 0.001, AT1R 1.00 (0.59) vs. 7.22 (4.14) R.U.; p < 0.001) and MasR (1.00 (0.70) vs. 4.52 (1.91) R.U.; p < 0.001), accompanied by increased expression of TNFα and ADAM17. These findings suggest that long-term T1D induces tissue-specific activation patterns of the RAS and inflammatory pathways within the cardiovascular system, which may contribute to the progression of diabetic cardiovascular complications. Therapeutic targeting of RAS components may represent a viable strategy for mitigating cardiovascular damage in T1D. Full article

Atherosclerosis is now recognized as a chronic inflammatory disease of the arterial wall, in which perivascular adipose tissue (PVAT) has evolved from a passive structural component to a key player in regulating vascular homeostasis and the pathophysiology of atherosclerosis, playing an active, not just structural, role. PVAT surrounds blood vessels and influences them metabolically, immunologically, and vascularly by secreting adipokines, cytokines, and other bioactive mediators. Under physiological conditions, PVAT has protective roles, as it produces adiponectin, nitric oxide (NO), and other vasodilatory factors that help maintain vascular tone and reduce inflammation. In particular, brown-like PVAT (rich in Uncoupling Protein-1 (UCP1) and mitochondria) offers significant vasoprotective effects. Under pathological conditions (obesity, dyslipidemia, insulin resistance), PVAT undergoes a phenotypic transition towards a pro-inflammatory profile by increasing leptin, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) secretion and decreasing adiponectin, contributing to endothelial dysfunction, vascular smooth muscle cell (VSMC) proliferation, local immune cell recruitment, extracellular matrix (ECM) remodeling, and fibrosis. PVAT plays a complex role in vascular health and disease, interacting with systemic metabolism through the secretion of bioactive molecules. Metabolic imbalances can promote PVAT inflammation. Epigenetic alterations and micro ribonucleic acid (miRNAs) can influence PVAT inflammation, and modern imaging methods for PVAT assessment, such as the fat attenuation index (FAI) and artificial intelligence-assisted radiomic profiling, may become predictive biomarkers of cardiac risk. Future directions aim to identify biomarkers and develop targeted therapies that modulate PVAT inflammation and dysfunction in the context of cardiovascular diseases. Full article

Aortic aneurysms (AAs), the dilation or widening of the aorta, lead to dissection or rupture with high morbidity and mortality if untreated. AA displays gender disparities in its prevalence, progression and outcomes, with women having worse outcomes and faster aneurysm growth. However, current guidelines do not address gender dimorphism, emphasizing the urgent need for personalized treatment strategies and further research. Perivascular adipose tissue (PVAT), a unique type of fat surrounding blood vessels, plays a critical role in maintaining vasomotor tone and vascular homeostasis, with dysfunction associated with chronic inflammation and vessel-wall remodeling. Indeed, PVAT dysfunction promotes the development of aortic aneurysms, with hormonal and biomechanical factors exacerbating the pathological vascular microenvironment. The sexually dimorphic characteristics of PVAT include morphological, immunological, and hormonally mediated differences. Thus, targeting PVAT-mediated mechanisms may be a promising option for the (gender-specific) therapeutic management of cardiovascular pathologies. This review examines the emerging importance of PVAT in vascular health, its potential therapeutic implications for AA, and identifies gaps in the current state of research. Full article

Cardiovascular diseases such as hypertension alter thoracic aorta structure. The role that the outer layer of the aorta, its perivascular adipose tissue (PVAT), plays in the pathogenesis of these alterations is poorly understood. In the descending thoracic aorta, PVAT is organized into three distinct strips: one located anterior to the aorta (AP) and two positioned laterally (LP). Genetic tracing indicates differences in the ontogeny of LP and AP, but the implications of these developmental differences and PVAT distribution on adipocyte development remain unknown. We hypothesize that the anatomical location of adipocyte progenitors influences their adipogenic potential and vasoactive functions. PVAT from LP and AP was collected from male SD rats at 10 wks of age (n = 7) to harvest adipocyte progenitors that were differentiated to adipocytes in adipogenic media. Adipogenesis was evaluated after induction and we performed next-generation RNA-seq on progenitors and adipocytes. We then employed Gene Set Enrichment Analysis for enrichment and network analyses. LP progenitors exhibited a 1.13-fold higher adipogenesis rate compared to those from AP. DEG analysis revealed LP had higher expression of adipogenic regulators and basal collagens Col4a2 and Col4a4. When challenged with angiotensin-II, adipocyte progenitors from LP maintained their adipogenic capacity and adipocytes from the same site maintained their secretion of adiponectin at higher rates than AP cells. However, treatment with a Piezo1 mechanoreceptor agonist reduced LP’s adipogenic capacity and diminished their adiponectin secretion. These findings highlight site-specific differences in adipogenic activity, extracellular matrix composition, and the secretion of the vasoactive adipokine adiponectin between the LP and AP PVAT strips of the thoracic aorta, suggesting potential functional distinctions in vascular health and disease. Full article

Background: Marfan syndrome (MFS) is a rare autosomal dominant disorder affecting connective tissues due to mutations in the fibrillin-1 gene. These genetic changes often result in severe cardiovascular conditions, including asymptomatic thoracic aortic dilation potentially leading to dissection or rupture. Perivascular adipose tissue attenuation (PVAT) observed on computed tomography may serve as a marker of localized inflammation and indicate early histopathological changes in the vascular walls of MFS patients compared to healthy individuals. Objective: This study aimed to compare PVAT values between patients with MFS and healthy controls in order to explore whether MFS patients show higher PVAT secondary to these histopathological abnormalities. Methods: This case–control study assessed PVAT on ascending aorta through computed tomography angiography (CTA) in 54 genetically confirmed MFS patients and 43 controls with low ischemic risk, excluding those with known aortic aneurysms. Results: PVAT analysis revealed significant differences between the MFS patients and healthy controls (−70.6 HU [−72.6 HU to −68.5 HU] versus −75.1 HU [−77.1 HU to −73.1 HU], p = 0.002), suggesting potential early vascular changes in the MFS group. Conclusions: The findings underscore the potential diagnostic role of PVAT in patients with genetically confirmed MFS but normal ascending aorta diameter. Full article

In obesity, recent research revealed that increased expression of the growth hormone secretagogue receptor (GHSR) in macrophages plays a pivotal role in the development of meta-inflammation, promoting macrophage infiltration and pro-inflammatory polarization. This study aimed to examine the association between GHSR-1a expression in atherosclerotic plaques and adjacent perivascular adipose tissue (PVAT) from 11 patients with obesity and peripheral artery disease (PAD) who underwent revascularization procedures. Immunohistochemistry was used to assess the expression of CD68, CD80, and CD14, while tissue homogenate levels of adiponectin, leptin, IL-6, and CRP were quantified via ELISA. Serum markers of inflammation were also measured. Among patients with GHSR-1a-positive (+) macrophages in atherosclerotic plaques, we observed significantly higher white blood cell counts and platelet-to-lymphocyte ratios in serum, a lower adiponectin-to-leptin ratio, and elevated IL-6 levels in both arterial and PVAT homogenates. Our findings suggest a link between GHSR-1a and macrophage/monocyte infiltration, macrophage polarization, and adipocytokine secretion in atherosclerotic plaques associated with obesity-induced PVAT dysfunction. Full article

Perivascular adipose tissue (PVAT) regulates vascular tone and is composed of adipocytes and several leukocyte subpopulations. Diet can modify PVAT function, as obesogenic diets cause morphological changes to adipocytes and skew the leukocyte phenotype, leading to PVAT dysregulation and impaired vasoregulation. Of note, platelets, the clot-forming cells, also modulate many facets of leukocyte activity, such as tissue infiltration and polarity. We aimed to determine whether platelets regulate the leukocyte populations residing within PVAT. Male C57Bl/6J mice were fed a Western diet (30% kcal sucrose, 40% kcal fat, 8.0% sodium) to develop obesogenic conditions for PVAT leukocyte remodeling. Diet was either administered acutely (2 weeks) or extended (8 weeks) to gauge the length of challenge necessary for remodeling. Additionally, platelet depletion allowed for the assessment of platelet relevance in PVAT leukocyte remodeling. Abdominal PVAT (aPVAT) and thoracic PVAT (tPVAT) were then isolated and leukocyte composition evaluated by flow cytometry. Compared to control, Western diet alone did not significantly impact PVAT leukocyte composition for either diet length. Platelet depletion, independent of diet, significantly disrupted PVAT leukocyte content with monocytes/macrophages most impacted. Furthermore, tPVAT appeared more sensitive to platelet depletion than aPVAT, providing novel evidence of platelet regulation of leukocyte composition within PVAT depots. Full article

We investigated the sex-dependent effects of inflammatory responses in visceral adipose tissue (VAT) and perivascular adipose tissue (PVAT), as well as hematological status, in relation to cardiovascular disorders associated with prediabetes. Using male and female hereditary hypertriglyceridemic (HHTg) rats—a nonobese prediabetic model featuring dyslipidemia, hepatic steatosis, and insulin resistance—we found that HHTg females exhibited more pronounced hypertriglyceridemia than males, while HHTg males had higher non-fasting glucose levels. Additionally, HHTg females had higher platelet counts, larger platelet volumes, and lower antithrombin inhibitory activity. Regarding low-grade chronic inflammation, HHTg males exhibited increased serum leptin and leukocyte levels, while females had increased serum interleukin-6 (IL-6). Both sexes had increased circulating plasminogen activator inhibitor-1 (PAI-1), higher PAI-1 gene expression in VAT and PVAT, and elevated intercellular adhesion molecule-1 (ICAM-1) gene expression in the aorta, contributing to endothelial dysfunction in the HHTg strain. However, HHTg females had lower tumor necrosis factor alpha (TNFα) gene expression in the aorta. Severe dyslipidemia in this prediabetic model was associated with hypercoagulation and low-grade chronic inflammation. The increase in PAI-1 expression in both VAT and PVAT seems to indicate a link between inflammation and vascular dysfunction. Despite the more pronounced dyslipidemia and procoagulation status in females, their milder inflammatory response may reflect an association between reduced cardiovascular damage and prediabetes. Full article

Pericoronary adipose tissue attenuation (PCAT_a), observed from coronary computed tomography angiography (CCTA), is emerging as an inflammation marker. This study evaluated the relationship between PCAT_a and plaque characteristics, including plaque type, burden, and coronary calcification. An observational study was conducted on 466 patients with suspected chronic coronary syndrome who underwent clinically indicated CCTA. PCAT_a was measured along the proximal 40 mm of the coronary arteries and averaged to represent the patient’s level. Plaque type was assessed, compositional plaque volumes were measured, and plaque burdens were quantified. The coronary calcification scores (CCSs) were categorized into groups. Statistical methods included t-tests, ANOVA, and multivariate regression analysis. PCAT_a differed significantly between calcified (−81.7 Hounsfield units (HU)) and soft (−77.5 HU) plaques. PCAT_a was positively associated with total plaque burden (β = 3.6) and non-calcified plaque burden (β = 7.0), but negatively correlated with calcified plaque burden (β = −3.5), independent of clinical factors and tube voltage (p < 0.05). The effect of PCAT_a was stronger when plaques of a different composition were absent. No significant differences in PCAT_a were found among different CCS groups. PCAT_a increased for calcified compared to soft plaques. The non-calcified plaque burden was associated with a higher PCAT_a, while the calcified plaque burden was associated with a lower PCAT_a. Full article

The perivascular adipose tissue (PVAT) regulates the arterial tone by releasing vasoactive molecules. PVAT dysfunction favoring the vasorelaxation response could contribute to the development of kidney disease in metabolic syndrome (MetS). Previously, we demonstrated that overactivation of angiotensin II signaling in the PVAT deteriorates the compensatory PVAT effects in rats with MetS (SHRSP.Z-Lepr^fa/IzmDmcr (SPZF) and SHR/NDmcr-cp (CP) rats). Apelin is an endogenous regulator of angiotensin II. Therefore, we investigated whether changes in apelin levels in the PVAT alter PVAT function and impair kidney function in MetS. Twenty-three-week-old male and female SPZF and CP rats were used. In the female CP rats, apelin mRNA levels in renal arterial PVAT, enhancing effects of the PVAT on acetylcholine-induced relaxation in renal arteries, and estimated glomerular filtration rate (eGFR) were the highest, and urine protein levels and homeostasis model assessment of insulin resistance (HOMA-IR) were the lowest. Apelin mRNA levels were positively correlated with the enhancing effects of the PVAT on vasorelaxation and eGFR but negatively correlated with urine protein levels and HOMA-IR. Moreover, apelin levels positively correlated with mRNA levels of angiotensin-converting enzyme 2 and angiotensin II type 1 receptor-associated protein, which are negative regulators of angiotensin II. This study suggests that a decline in apelin levels in the PVAT, probably owing to angiotensin II, is associated with PVAT dysfunction on vascular tone, resulting in impaired kidney function in MetS. Full article

Background/Objectives: Perivascular adipose tissue (PVAT) exerts a paracrine effect on blood vessels and our objective was to understand PVAT molecular signatures related to cardiovascular disease. Methods: We studied two groups: those undergoing mitral valve repair/replacement (VR, n = 16) and coronary artery bypass graft (CABG, n = 38). VR donors did not have coronary artery disease, whereas CABG donors had advanced coronary artery disease. Clinical and tissue pathologies and proteomics from adipose tissue were assessed. Results: Donors undergoing VR had a lower body mass index (p = 0.01), HbA1C (p = 0.0023), and incidence of diabetes (p = 0.022) compared to CABG. VR donors were overall healthier, with higher cardiac function compared to CABG donors, based on ejection fraction. Although adipose histopathology between groups was not markedly different, PVAT had smaller and more adipocytes compared to subcutaneous adipose tissues. These differences were validated by whole specimen automated morphological analysis, and anisotropy analysis showed small (2.8–7.5 μm) and large (22.8–64.4 μm) scale differences between perivascular and subcutaneous adipose tissue from CABG donors, and small scale changes (2.8–7.5 μm) between perivascular and subcutaneous adipose tissue from VR donors. Distinct protein signatures in PVAT and subcutaneous adipose tissue include those involved in secretion, exosomes and vesicles, insulin resistance, and adipocyte identity. Comparing PVAT and subcutaneous adipose tissue from CABG donors, there were 82 significantly different proteins identified with log fold change ≥ 0.3 or ≤−0.3 (p < 0.05). Using this threshold, there were 36 differences when comparing PVAT and subcutaneous adipose tissue from VR donors, 58 differences when comparing PVAT from CABG or VR donors, and 55 when comparing subcutaneous adipose tissue from CABG vs. VR donors. Conclusions: Routine histopathology cannot differentiate between PVAT from donors with or without coronary artery disease, but multiscale anisotropy analysis discriminated between these populations. Our mass spectrometry analysis identified a cohort of proteins that distinguish between adipose depots, and are also associated with the presence or absence of coronary artery disease. Full article

Inflammatory Bowel Diseases (IBDs) are associated with aberrant immune function, widespread inflammation, and altered intestinal blood flow. Perivascular adipose tissue (PVAT) surrounding the mesenteric vasculature can modulate vascular function and control the local immune cell population, but its structure and function have never been investigated in IBD. We used an IL10^−/− mouse model of colitis that shares features with human IBD to test the hypothesis that IBD is associated with (1) impaired ability of PVAT to dilate mesenteric arteries and (2) changes in PVAT resident adipocyte and immune cell populations. Pressure myography and electrical field stimulation of isolated mesenteric arteries show that PVAT not only loses its anti-contractile effect but becomes pro-contractile in IBD. Quantitative immunohistochemistry and confocal imaging studies found significant adipocyte hyperplasia and increased PVAT leukocytes, particularly macrophages, in IBD. PCR arrays suggest that these changes occur alongside the altered cytokine and chemokine gene expression associated with altered NF-κB signaling. Collectively, these results show that the accumulation of macrophages in PVAT during IBD pathogenesis may lead to local inflammation, which ultimately contributes to increased arterial constriction and decreased intestinal blood flow with IBD. Full article