Aortic Intima-media Thickness Research Articles

Arterial structure and function in children with inflammatory bowel disease.

People with inflammatory bowel disease (IBD) have an increased risk of cardiovascular disease, including in younger adulthood. This may arise in part from chronic, systemic low-grade inflammation. The process of atherosclerosis may begin in childhood. We sought to determine whether pediatric IBD is associated with adverse changes in arterial structure and function as a marker of early increased cardiovascular risk. We performed a case-control study comparing children with IBD for a median disease duration of 2.49 (interquartile range 1.23, 4.38) years with healthy children. In a single visit, we collected baseline clinical and anthropometric data, and measured blood pressure, pulse wave velocity, carotid artery distensibility, and aortic and carotid intima-media thickness. High-sensitivity C-reactive protein and fasting lipids were measured. We enrolled 81 children with IBD (40 with Crohn's disease, 40 with ulcerative colitis, and 1 with unspecified IBD) and 82 control participants. After adjusting for age, sex, body mass index z-score, blood pressure, and low-density lipoprotein cholesterol, there was no difference in measures of arterial structure and function in children with IBD compared with controls, nor between those with Crohn's disease or ulcerative colitis. We did not show any differences in arterial structure and function in children with a history of IBD for less than 5 years compared with healthy controls. IBD diagnosed in childhood may provide a window of opportunity to actively reduce standard cardiovascular risk factors and improve future cardiovascular outcomes.

Effects of methotrexate, <em>Moringa oleifera</em>, and <em>Andrographis paniculata</em> extracts on the myocardial and aortic tissue of streptozotocin-nicotinamide-induced hyperglycemic rats

BACKGROUND Methotrexate (MTX) could lower glucose levels in type 1 diabetes mellitus, while Moringa oleifera and Andrographis paniculata supplementations have similar effects on hyperglycemia. This study aimed to analyze the effects of MTX, M. oleifera, and A. paniculata leaf extracts on the myocardial interleukin (IL)-6 and the histopathology of the left ventricle and aorta.
 METHODS 49 rats were divided equally into 7 groups: negative control and diabetic induced by streptozotocin-nicotinamide (STZ-NA) injection consisting of positive control (STZ-NA only), M. oleifera (500 mg/kgBW/day), A. paniculata (500 mg/kgBW/day), MTX (7 mg/kgBW/week), MTX (7 mg/kgBW/week)+M. oleifera (500 mg/kgBW/day), and MTX (7 mg/kgBW/week)+A. paniculata (500 mg/kgBW/day). We analyzed oral MTX, M. oleifera, and A. paniculata leaf extracts’ effects on random blood glucose, myocardial IL-6, and cardiac histopathology of STZ-NA-induced hyperglycemic male rats. Data were analyzed using Wilcoxon and Kruskal–Wallis tests.
 RESULTS Myocardial IL-6 in the M. oleifera group was significantly lower compared to the positive control group (p = 0.041). Compared to the positive control group, the myocardial necrosis and aortic intima–media thickness in the MTX+A. paniculata group were significantly reduced (p = 0.005 and 0.001, respectively).
 CONCLUSIONS MTX, M. oleifera, and A. paniculata showed antihyperglycemic effect, both individually and in combination. A. paniculata leaf extract had a significant cardioprotective effect in STZ-NA-induced hyperglycemia.

Cardioprotective and Antifibrotic Effects of Low-Dose Renin-Angiotensin-Aldosterone System Inhibitors in Type 1 Diabetic Rat Model.

Diabetic cardiovascular complications are associated with up to 50% mortality, and current therapies are not effective enough. Renin-angiotensin-aldosterone system inhibitors (RAASis) are the standard of care for diabetic patients with hypertension and albuminuria. Based on our previous studies reporting the renoprotective effects of low-dose RAASis, here, we hypothesized that low-dose RAASi treatment has cardioprotective and antifibrotic benefits in type 1 diabetes mellitus (T1DM). After five weeks of T1DM, adult male Wistar rats received low doses of ramipril, losartan, or eplerenone for two weeks. Heart rate, blood pressure, and pulse wave velocity (PWV) were recorded. Aortic intima-media thickness (IMT), collagen accumulation, and myocardial fibrosis were assessed. All RAASis reduced PWV elevation, prevented the progression of myocardial fibrosis, and normalized B-type natriuretic peptide, troponin I, and fibroblast growth factor 23 levels without affecting blood pressure. Interestingly, only eplerenone reversed the decline in Klotho levels and reduced IMT and fibrosis in the media of the aorta. Our comparative analysis suggests that mineralocorticoid receptor antagonists, particularly eplerenone, may offer superior efficacy in halting both the arterial and the myocardial injuries in T1DM compared to angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers.

Acute effects of cigarette smoke on Endothelial Nitric Oxide synthase, vascular cell adhesion molecule 1 and aortic intima media thickness.

Background. Cigarette smoking could induce endothelial dysfunction and the increase of circulating markers of inflammation by activation of monocytes. This can lead to increased intima media thickness (IMT) of entire blood vessels and result in acceleration of the atherosclerosis process. However, to our knowledge, little is known about the role of cigarette smoking in this atherosclerotic inflammatory process. The aim of this study is to explore the link between cigarette smoking and its effect on endothelial nitric oxide synthase (e-NOS) and vascular cell adhesion molecule 1 (VCAM-1). Methods. An experimental study with a post-test only controlled group design was used. We used 18 Wistar rats ( Rattus norvegicus) randomly subdivided into two groups: group K (-) were not exposed to tobacco smoke, whereas group K (+) were exposed to smoke equivalent of more than 40 cigarettes for 28 days daily. After 28 days, samples were analyzed for e-NOS, VCAM-1 and aortic IMT. Results . Our results indicate that tobacco smoke can enhance the expression of VCAM-1 on rat cardiac vascular endothelial cells, resulting in a decreased expression of e-NOS level and increase of aortic IMT. Linear regression model found that eNOS level negatively correlated wiith aortic IMT ( r 2 = 0.584, β = -0.764, p < 0.001), whereas VCAM-1 expression did not correlate with aortic IMT ( r 2 = 0.197, p = 0.065). Conclusion. Low e-NOS level and high VCAM-1 level observed after cigarette smoke exposure which may increase aortic IMT.

Cardiovascular Calcifications Are Correlated with Inflammation in Hemodialysis Patients.

Background and Objectives: The main cause of morbidity and mortality in hemodialysis patients is cardiovascular disease, which is quite common. The main objective of our study was to investigate the relationship between oxidative stress, inflammation, and vascular and valvular calcifications in hemodialysis patients. Materials and Methods: This observational study had 54 hemodialysis patients, with an average age of 60.46 ± 13.18 years. Cardiovascular ultrasound was used to detect and/or measure aortic and mitral valve calcifications, carotid and femoral atheroma plaques, and common carotid intima-media thickness. The aortic calcification score was determined using a lateral abdomen plain radiograph. The inflammatory, oxidative, metabolic, and dietary statuses, as well as demographic characteristics, were identified. Results: There were significant correlations between the levels of IL-6 and carotid plaque number (p = 0.003), fibrinogen level and aortic valve calcifications (p = 0.05), intima-media thickness (p = 0.0007), carotid plaque number (p = 0.035), femoral plaque number (p = 0.00014), and aortic calcifications score (p = 0.0079). Aortic annulus calcifications (p = 0.03) and intima-media thickness (p = 0.038) were adversely linked with TNF-α. Nutrition parameters were negatively correlated with atherosclerosis markers: number of carotid plaques with albumin (p = 0.013), body mass index (p = 0.039), and triglycerides (p = 0.021); number of femoral plaques with phosphorus (0.013), aortic calcifications score with albumin (p = 0.051), intima-media thickness with LDL-cholesterol (p = 0.042). Age and the quantity of carotid plaques, femoral plaques, and aortic calcifications were linked with each other (p = 0.0022, 0.00011, and 0.036, respectively). Aortic annulus calcifications (p = 0.011), aortic valve calcifications (p = 0.023), and mitral valve calcifications (p = 0.018) were all associated with an increased risk of death. Conclusions: Imaging measures of atherosclerosis are adversely connected with dietary status and positively correlated with markers of inflammation and risk of mortality.

Assessment of Vascular Indices by Abdominal Aortic Ultrasonography in Preterm Neonates with Bronchopulmonary Dysplasia.

Preterm infants with bronchopulmonary dysplasia (BPD) frequently encounter systemic hypertension, yet the underlying cause remains elusive. Given the absence of prior investigations concerning the correlation between systemic hypertension and aortic thickness, we undertook this study to assess and juxtapose diverse vascular indices amidst preterm neonates with BPD, preterm neonates lacking BPD, and healthy neonates, utilizing abdominal aorta ultrasonography. This cross-sectional study encompassed 20 preterm neonates, 20 preterm neonates with BPD, and 20 healthy neonates, meticulously matched for sex and postnatal age. Comprehensive demographic, anthropometric, and clinical evaluation data were documented. The neonates underwent abdominal aortic ultrasonography for comparative evaluation of aortic wall thickness and vasomotor function across the three groups. The study revealed that neonates with BPD exhibited a notably higher average systolic blood pressure than preterm and term neonates (P < 0.05). Conversely, echocardiographic parameters such as input impedance, and arterial wall stiffness index displayed no substantial variance among the three groups (P > 0.05). The mean (SD) aortic intima-media thickness (aIMT) for preterm neonates with BPD, preterm neonates, and term neonates were 814 (193.59) μm, 497.50 (172.19) μm, and 574.00 (113.20) μm, correspondingly (P < 0.05). Furthermore, the mean (SD) pulsatile diameter for preterm neonates with BPD, preterm neonates, and term neonates were 1.52 (0.81) mm, 0.91 (0.55) mm, and 1.34 (0.51) mm, respectively (P < 0.05). Following adjustment for birth weight, sex, and gestational age at birth, the study identified a noteworthy correlation between aIMT and BPD. The investigation concluded that the mean aortic intima-media thickness (aIMT) was significantly elevated in preterm neonates with BPD, signifying a potential early indicator of atherosclerosis and predisposition to future heightened blood pressure and cardiovascular ailments. Consequently, the study postulates that aIMT could be a consistent and well-tolerated marker for identifying BPD patients at risk of developing these health complications.

Black cumin ethanolic extract reduce aortic intima media thickness due to cigarette smoke exposure in experimental rats

Black cumin ethanolic extract reduce aortic intima media thickness due to cigarette smoke exposure in experimental rats

Acute effects of cigarette smoke on Endothelial Nitric Oxide synthase, vascular cell adhesion molecule 1 and aortic intima media thickness

Background. Cigarette smoking could induce endothelial dysfunction and the increase of circulating markers of inflammation by activation of monocytes. This can lead to increased intima media thickness (IMT) of entire blood vessels and result in acceleration of the atherosclerosis process. However, to our knowledge, little is known about the role of cigarette smoking in this atherosclerotic inflammatory process. The aim of this study is to explore the link between cigarette smoking and its effect on endothelial nitric oxide synthase (e-NOS) and vascular cell adhesion molecule 1 (VCAM-1). Methods. An experimental study with a post-test only controlled group design was used. We used 18 Wistar rats (Rattus norvegicus) randomly subdivided into two groups: group K (-) were not exposed to tobacco smoke, whereas group K (+) were exposed to smoke equivalent of more than 40 cigarettes for 28 days daily. After 28 days, samples were analyzed for e-NOS, VCAM-1 and aortic IMT. Results. Our results indicate that tobacco smoke can enhance the expression of VCAM-1 on rat cardiac vascular endothelial cells, resulting in a decreased expression of e-NOS level and increase of aortic IMT. Linear regression model found that eNOS level negatively correlated wiith aortic IMT (r2 = 0.584, β = -0.764, p &lt; 0.001), whereas VCAM-1 expression did not correlate with aortic IMT (r2 = 0.197, p = 0.065). Conclusion. Low e-NOS level and high VCAM-1 level observed after cigarette smoke exposure which may increase aortic IMT.

Impact of perinatal factors on biomarkers of cardiovascular disease risk in preadolescent children.

This review aims to summarize associations of the perinatal environment with arterial biophysical properties in childhood, to elucidate possible perinatal origins of adult cardiovascular disease (CVD). A systematic search of PubMed database was performed (December 2020). Studies exploring associations of perinatal factors with arterial biophysical properties in children 12 years old or less were included. Properties studied included: pulse wave velocity; arterial stiffness or distensibility; augmentation index; intima-media thickness of aorta (aIMT) or carotids; endothelial function (laser flow Doppler, flow-mediated dilatation). Two reviewers independently performed study selection and data extraction. Fifty-two of 1084 identified records were included. Eleven studies explored associations with prematurity, 14 explored maternal factors during pregnancy, and 27 explored effects of low birth weight, small-for-gestational age and foetal growth restriction (LBW/SGA/FGR). aIMT was consistently higher in offspring affected by LBW/SGA/FGR in all six studies examining this variable. The cause of inconclusive or conflicting associations found with other arterial biophysical properties and perinatal factors may be multifactorial: in particular, measurements and analyses of related properties differed in technique, equipment, anatomical location, and covariates used. aIMT was consistently higher in LBW/SGA/FGR offspring, which may relate to increased long-term CVD risk. Larger and longer term cohort studies may help to elucidate clinical significance, particularly in relation to established CVD risk factors. Experimental studies may help to understand whether lifestyle or medical interventions can reverse perinatal changes aIMT. The field could be advanced by validation and standardization of techniques assessing arterial structure and function in children.

Effects of Melatonin Supplementation on the Aortic Wall in a Diet-Induced Obesity Rat Model.

Background Cardiovascular disease (CVD) is still the leading cause of death globally. Alterations in the arterial wall architecture predict CVD morbidity and mortality and are associated with other CVD risk factors. Aortic wall thickness is closely linked to short- and long-term CVD morbidity and mortality, even without pronounced atherosclerotic changes.Obesity increases the risk of a broad spectrum of pathologies with vascular manifestation,which are oftenpathogenically associated with chronic oxidative stress and inflammatory response. Hence, as an antioxidant and anti-inflammatory agent, the pineal gland hormone melatonin is expected to have vasoprotective effects. This study evaluated the effects of melatonin supplementation on aortic wall thickness by assessing the cross-sectional associations of abdominal obesity with aortic intima-media thickness in a diet-induced obesity rat model. Methodology The model comprised of male Wistar rats that were on a high-fructose diet (HFD) (20% glucose-fructose corn syrup) for 12 weeks; the rats were divided into four groups (n = 8): control, HFD, HFD and melatonin supplementation (per os- 4 mg/kg/24h), and control and melatonin supplementation. All rats received a standard rodent diet and tap water. Zoometric measurements and the Lee index were calculated. Morphometric analysis of the abdominal aorta was performed by staining with hematoxylin-eosin and measuring the thickness of the abdominal aortic wall. For this, we used the Aperio Image Scope software. To evaluate the functional properties of the abdominal aorta, the modified Kernogan's index (KI) was employed. Results The results showed significantly elevated body weight (Lee index), KI, and wall thickness of the aorta abdominalis with morphometric changes in the vessel wall in HFD rats compared to the control group. Melatonin supplementation prevented these changes. Conclusions The administration of HFD to Wistar rats led to pathomorphological and morphometric changes in their abdominal aorta, which constitute the main diagnostic criteria of endothelial dysfunction. Melatonin supplementation regressed vascular wall remodeling and restored its functional capacity.

Effect of Combination of Purple Sweet Potato (Ipomoea batatas L.) Ethanolic Extract and Ramipril Administration on Myocardial C-Reactive Protein Expression and Aortic Intima-Media Thickness in Hypertensive Rat Model

Purposes: To determine the effect of giving a combination of purple sweet potato (Ipomoea batatas L.) ethanolic extract and ramipril in a rat model of hypertension. Methods: This is an experimental study with a post-test-only control group design and is a collaborative study of the effect of giving a combination of purple sweet potato (Ipomoea batatas L.) ethanolic extract and ramipril in a rat model of hypertension. Thirty male Wistar rats were given 2 mL/day of a 4% NaCl diet to induce hypertension. The rats were divided into three treatment groups, consists of NaCl 4% 2 mL/day + combination therapy with purple sweet potato (Ipomoea batatas L.) ethanolic extract 400 mg/kgBW/day and ramipril 1 mg/day (P1), NaCl 4% 2 mL/day + purple sweet potato (Ipomoea batatas L.) ethanolic extract 400 mg/kgBW/day (P2) and NaCl 4% 2 mL/day + ramipril 1 mg/day (P3). At week 5, the rat was executed to examine myocardial CRP expression and measure aortic IMT. All the data obtained were analyzed statistically. Results: There was a significant difference in myocardial CRP expression between the three treatment groups (p value&lt;0.05). The combination of purple sweet potato (Ipomoea batatas L.) ethanolic extract 400 mg/kgBW/day + ramipril 1 mg/day (P1) showed a better effect on reducing myocardial CRP expression than administration of purple sweet potato (Ipomoea batatas L.) ethanolic extract 400 mg/kgBW/day (P2) (mean difference 216.44 ng/ml; 95% CI 133.56 – 299.32; p value&lt;0.001) or Ramipril 1 mg/day (P3) (mean difference 144.44 ng/ml; 95% CI 29 .40 – 199.47; p value=0.010). Administration of Ramipril 1 mg/day (P3) showed a better effect on reducing myocardial CRP expression than the group given purple sweet potato (Ipomoea batatas L.) ethanolic extract 400 mg/kg/day (P2) (mean difference 102.00 ng/ml; CI 95% 19 .11 – 184.88; p value=0.018). There was a significant difference in aortic IMT between the three treatment groups (p value&lt;0.05). The combination of purple sweet potato (Ipomoea batatas L.) ethanolic extract 400 mg/kgBW/day + ramipril 1 mg/day (P1) showed a better effect on reducing aortic IMT than administration of purple sweet potato (Ipomoea batatas L.) ethanolic extract 400 mg/kgBW/day (P2) (mean difference 10,16 μm; 95% CI 6,63 – 13,69; p value&lt;0.001) or Ramipril 1 mg/day (P3) (mean difference 5,10 μm; 95% CI 1,40 – 8,70; p value=0.008). Administration of Ramipril 1 mg/day (P3) showed a better effect on reducing aortic IMT than the group given purple sweet potato (Ipomoea batatas L.) ethanolic extract 400 mg/kg/day (P2) (mean difference 5,05 μm; CI 95% 1,50 – 8,50; p value=0.007). Combination of purple sweet potato (Ipomoea batatas L.) ethanolic extract and ramipril showed a higher potential effect on reducing myocardial CRP expression and aortic IMT compared to single therapy. Conclusion: The combination of purple sweet potato (Ipomoea batatas L.) ethanolic extract 400 mg/kgBW/day + ramipril 1 mg/day can provide the best decrease in the expression of myocardial CRP and aortic IMT compared to the administration of purple sweet potato (Ipomoea batatas L.) ethanolic extract 400 mg/kg/day or ramipril 1 mg/day.

Intrauterine exposure to preeclampsia does not impair vascular health in children.

Preeclampsia is a serious multisystem blood pressure disorder during pregnancy that is associated with increased long-term risk of cardiovascular disease to the mother and offspring. We investigated the vascular health of children exposed to intrauterine preeclampsia. This was a cross-sectional study of offspring in a prospective cohort of women with complications during pregnancy. Children aged between 2 and 5 years [median age 4.7 (2.8, 5.1) years] exposed to intrauterine preeclampsia (n = 26) or normotensive controls (n = 34), were recruited between July 2020 and April 2021. Vascular health was assessed by measuring aortic intima-media thickness and pulse wave velocity. Univariate generalized linear regression models were used to explore associations between vascular measurements and explanatory variables. Children exposed to preeclampsia had a lower body mass index at assessment (15.5 vs. 16.2 kg/m2, p = 0.04), birth weight (2.90 vs. 3.34 kg, p = 0.004), gestational age at birth (37.5 vs. 39.4 weeks, p < 0.001) and higher frequency of preterm birth (27% vs. 6%, p = 0.02). There were no differences in vascular health between children exposed to preeclampsia vs. controls (mean aortic intima-media thickness 0.575 mm vs. 0.563 mm, p = 0.51, pulse wave velocity 4.09 vs. 4.18 m/s, p = 0.54) and there were no significant associations in univariate analyses. There were no major adverse differences in vascular health which contrasts with existing studies. This suggests exposure to intrauterine preeclampsia may result in a less severe cardiovascular phenotype in young children. While reassuring, longitudinal studies are required to determine if and when exposure to intrauterine preeclampsia affects vascular health in children.

Acute effects of cigarette smoke on Endothelial Nitric Oxide synthase, vascular cell adhesion molecule 1 and aortic intima media thickness

Background. Cigarette smoking could induce endothelial dysfunction and the increase of circulating markers of inflammation by activation of monocytes. This can lead to increased intima media thickness (IMT) of entire blood vessels and result in acceleration of the atherosclerosis process. However, to our knowledge, little is known about the role of cigarette smoking in this atherosclerotic inflammatory process. The aim of this study is to explore the link between cigarette smoking and its effect on endothelial nitric oxide synthase (e-NOS) and vascular cell adhesion molecule 1 (VCAM-1). Methods. An experimental study with a post-test only controlled group design was used. We used 18 Wistar rats (Rattus norvegicus) randomly subdivided into two groups: group K (-) were not exposed to tobacco smoke, whereas group K (+) were exposed to smoke equivalent of more than 40 cigarettes for 28 days daily. After 28 days, samples were analyzed for e-NOS, VCAM-1 and aortic IMT. Results. Our results indicate that tobacco smoke can enhance the expression of VCAM-1 on rat cardiac vascular endothelial cells, resulting in a decreased expression of e-NOS level and increase of aortic IMT. Linear regression model found that eNOS level negatively correlated wiith aortic IMT (r2 = 0.584, β = -0.764, p &lt; 0.001), whereas VCAM-1 expression did not correlate with aortic IMT (r2 = 0.197, p = 0.065). Conclusion. Low e-NOS level and high VCAM-1 level observed after cigarette smoke exposure which may increase aortic IMT.

Triglyceride glucose index is independently associated with aortic intima-media thickness in patients without known atherosclerotic cardiovascular disease or diabetes.

Background: The triglyceride-glucose (TyG) index is a reliable marker of insulin resistance. We aimed to investigate the relationship between the TyG index and aortic intima-media thickness (IMT) in individuals without diabetes mellitus and atherosclerotic cardiovascular disease undergoing transoesophageal echocardiography due to suspected structural heart disease.Methods: One hundred twenty-two patients enrolled in the study between January 2021 and June 2021. Patients were divided into two groups according to their median IMT; patients with an IMT equal to or less than 1.42 mm were low IMT group, and higher than 1.42 mm were high IMT group. Triglyceride-glucose index were higher in the high IMT group (8.69 ± 0.59 vs. 8.37 ± 0.53, p = .003).Results: Triglyceride-glucose index was correlated with IMT (r = 0.259, p = .005) and in binary logistic regression analysis age and TyG was independently associated with having high IMT (β = 0.076, exp(B)=1.079 95%CI = 1.041–1.118, p < .001 and β = 0.847, exp(B)= 2.334 95%CI= 1.048–5.199, p = .038, respectively).Conclusion: We found an independent relationship between TyG and IMT of the thoracic aorta, an early marker of subclinical atherosclerosis in patients without known atherosclerotic cardiovascular disease or diabetes. Therefore, the TyG index can identify high-risk subjects in the general population.

Inflammatory Role of Milk Fat Globule-Epidermal Growth Factor VIII in Age-Associated Arterial Remodeling.

BackgroundAge‐associated aortic remodeling includes a marked increase in intimal medial thickness (IMT), associated with signs of inflammation. Although aortic wall milk fat globule–epidermal growth factor VIII (MFG‐E8) increases with age, and is associated with aortic inflammation, it is not known whether MFG‐E8 is required for the age‐associated increase in aortic IMT. Here, we tested whether MFG‐E8 is required for the age‐associated increase in aortic IMT.Methods and ResultsTo determine the role of MFG‐E8 in the age‐associated increase of IMT, we compared aortic remodeling in adult (20‐week) and aged (96‐week) MFG‐E8 (−/−) knockout and age matched wild‐type (WT) littermate mice. The average aortic IMT increased with age in the WT from 50±10 to 70±20 μm (P<0.0001) but did not significantly increase with age in MFG‐E8 knockout mice. Because angiotensin II signaling is implicated as a driver of age‐associated increase in IMT, we infused 30‐week‐old MFG‐E8 knockout and age‐matched littermate WT mice with angiotensin II or saline via osmotic mini‐pumps to determine whether MFG‐E8 is required for angiotensin II–induced aortic remodeling. (1) In WT mice, angiotensin II infusion substantially increased IMT, elastic lamina degradation, collagen deposition, and the proliferation of vascular smooth muscle cells; in contrast, these effects were significantly reduced in MFG‐E8 KO mice; (2) On a molecular level, angiotensin II treatment significantly increased the activation and expression of matrix metalloproteinase type 2, transforming growth factor beta 1, and its downstream signaling molecule phosphorylated mother against decapentaplegic homolog 2, and collagen type I production in WT mice; however, in the MFG‐E8 knockout mice, these molecular effects were significantly reduced; and (3) in WT mice, angiotensin II increased levels of aortic inflammatory markers phosphorylated nuclear factor‐kappa beta p65, monocyte chemoattractant protein 1, tumor necrosis factor alpha, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 molecular expression, while in contrast, these inflammatory markers did not change in knockout mice.ConclusionsThus, MFG‐E8 is required for both age‐associated proinflammatory aortic remodeling and also for the angiotensin II–dependent induction in younger mice of an aortic inflammatory phenotype observed in advanced age. Targeting MFG‐E8 would be a novel molecular approach to curb adverse arterial remodeling.

Early Life Determinants of Vascular Structure in Fetuses, Infants, Children, and Adolescents: A Systematic Review and Meta-Analysis

To investigate the association between early life exposures during the first 1000days (conception to age 24months) and aortic intima-media thickness (aIMT), an early indicator of cardiovascular disease (CVD) risk, in youths. The MEDLINE, Embase, Scopus, CINAHL, and Allied and Complementary Medicine databases were searched from inception to July 2021. Eligibility criteria included observational controlled studies in youths aged <20years with risk factors/exposures during the first 1000days and aIMT measurements (unadjusted mean±SD). Outcome data were pooled using a random-effects meta-analysis. Meta-regression was used to investigate confounders. A total of 8657 articles were identified, of which 34 were included in our meta-analysis. The age of participants ranged from 22.9weeks gestation in utero to 10.9years. In the meta-analysis (n=1220 cases, n=1997 controls), the following factors were associated with greater aIMT: small for gestational age (SGA) status (14 studies, mean difference, 0.082mm; 95% CI, 0.051-0.112; P<.001; I2=97%), intrauterine growth restriction (6 studies; mean difference, 0.198mm, 95% CI, 0.088-0.309; P<.001; I2=97%), preeclampsia (2 studies; mean difference, 0.038mm; 95% CI, 0.024-0.051; P<.001; I2=38%), and large for gestational age (LGA) status (3 studies; mean difference, 0.089mm; 95% CI, 0.043-0.0136; P<.001; I2=93%). In meta-regression, older age (P<.001), higher prevalence of maternal smoking (P=.04), and SGA (P<.001) were associated with greater difference in aIMT in preterm participants compared with controls. Limitations included the high heterogeneity present in most meta-analyses and the scope of our meta-regression. Adverse early life exposures are associated with greater aIMT in youths, consistent with an increased risk for CVD later in life. Further research is needed to determine whether intervention and preventive strategies deliver clinical benefits to improve future cardiovascular health.

Early life determinants of vascular structure in foetuses, infants, children and adolescents: A systematic review and meta-analysis

Background and Aims : The first 1,000 days of life shape lifelong health, including cardiovascular disease (CVD) risk. Aortic intima-media thickness (aIMT), a measure of subclinical atherosclerosis, is an early indicator of CVD, amenable to change from as early as in-utero. We investigated the association between early life risk factors/exposures during the first 1,000 days and aIMT in youth.

Aumento da Espessura Médio-intimal Aórtica e sua Relação com Estresse Oxidativo Elevado em Pacientes com Talassemia Menor

ResumoFundamento A espessura médio-intimal (EMI) da artéria aorta abdominal (EMI-A) pode ser um marcador precoce de aterosclerose subclínica e um indicador objetivo de estresse oxidativo em pacientes com talassemia menor.Objetivo Avaliar se as EMIs da artéria aorta e da artéria carótida (EMI-C) se alteram com estresse oxidativo, e examinar a relação entre esses parâmetros em pacientes com talassemia menor.Métodos O estudo incluiu 80 pacientes diagnosticados com talassemia menor, e 50 indivíduos sadios com idade e sexo similares. Após procedimentos de rotina, as amostras de sangue foram coletadas dos grupos de estudo para a medida da homeostase tiol/dissulfeto e da albumina modificada pela isquemia (AMI). As medidas da EMI-C foram realizadas a partir de quatro regiões diferentes (artéria carótida externa direita e esquerda e artéria carótida interna direita e esquerda) por ultrassonografia, e a medida da EMI-A foi realizada por ultrassonografia abdominal. Um valor de p<0,05 foi definido como estatisticamente significativo.Resultados Nos pacientes com talassemia menor, os níveis de tiol nativo e tiol total, e a razão tiol nativo/tiol total foram mais baixos, e os valores de AMI, razão dissulfeto/tiol nativo, e razão dissulfeto/tiol total foram mais altos que no grupo controle. A EMI-A foi significativamente maior no grupo de pacientes com talassemia menor que nos controles (1,46±0,37 vs 1,23±0,22 e p<0,001). Quando os parâmetros associados com EMI-A na análise univariada foram avaliados por regressão linear multivariada, EMI-A apresentou uma relação positiva, e os níveis de tiol nativo e tiol total apresentaram uma forte relação negativa com AMI (p<0,01).Conclusão Nós demonstramos, pela primeira vez, um aumento no estresse oxidativo com a elevação da EMI-A, e valores inalterados da EMI-C em pacientes com talassemia menor.

VE-cadherin cleavage in obstructive sleep apnea syndrome: Signalling pathway and proteases as anti-atherogenic targets

Cardiovascular complications of obstructive sleep apnea syndrome (OSA), such as atherosclerosis, are a real public health concern. They result from endothelial dysfunction induced by intermittent hypoxia (IH). VE-cadherin (VE-cad) undergoes IH-induced cleavage leading to be a biomarker of endothelial dysfunction in several pathologies (sVE). Our hypothesis is that, in OSA, VE-cad cleavage would contribute to the onset of endothelial permeability, resulting in endothelial dysfunction and atherosclerosis. Our aim is to characterize the signalling pathway and proteases that perform VE-cad cleavage in a cellular model of IH and determine if blocking VE-cad cleavage in vitro and in vivo could inhibit IH-induced atherogenesis. Human Aortic Endothelial Cells (HAEC) monolayers were exposed to 6 h IH and treated with tyr-kinase inhibitors (Saracatinib, Pazopanib), HIF-1 inhibitor (Acriflavine) and protease's inhibitors. Candidate proteases (MMP2, PCSK9 and ADAM10) were identified by performing a human protease array in OSA patient's sera. Endothelial permeability was assessed by measuring FITC-Dextran permeability and monocyte passage. VE-cad cleavage was studied by measuring sVE in cells’ supernatants. Vascular remodeling and VE-cad regulation were studied in C57BL/6 mice (2 weeks IH), atherosclerotic plaques and arterial pressure were studied in ApoE-/- mice (8 weeks IH), both treated with tyr-kinase and HIF-1 inhibitors. In our IH cellular model, VE-cad cleavage and endothelial permeability increased. These effects were reversed by the HIF-1 and tyr-kinase inhibitors and the proteases’ inhibitors. In vivo, IH increased aorta intima-media thickness and sVE serum level, and decreased VE-cad expression in the endothelium of mice. In ApoE-/- mice, IH increased atherosclerotic plaques formation. These effects were blocked by inhibitors of VE-cad cleavage signaling pathway ( Fig. 1 ). We suggest that IH increases endothelial permeability by inducing VE-cad cleavage via the HIF-1 and tyr-kinase pathways, and possibly involving MMP2, PCSK9 and/or ADAM10 proteases. Blocking VE-cad cleavage prevents vascular remodeling and atherosclerotic plaques formation which suggests that VE-cad could be a potential target to a new anti-atherogenesis strategy.

The Assessment of Maternal and Fetal Intima-Media Thickness in Perinatology.

Intima-media thickness (IMT) measurement is a non-invasive method of arterial wall assessment. An increased IMT is a common manifestation of atherosclerosis associated with endothelial dysfunction. In the course of pregnancy, various maternal organs, including the endothelium, are prepared for their new role. However, several pre-gestational conditions involving endothelial dysfunction, such as diabetes, chronic hypertension, and obesity, may impair the adaptation to pregnancy, whereas vascular changes may also affect fetal development, thus, influencing the fetal IMT. In the conducted studies, a correlation was found between an increased fetal abdominal aorta IMT (aIMT) and placental dysfunctions, which may subsequently impact both the mother and the fetus, and contribute to gestational hypertension, preeclampsia (PE), and fetal growth restriction (FGR). In fact, data indicate that following the delivery, the endothelial dysfunction persists and influences the future health of the mother and the newborn. Hypertensive disorders in pregnancy increase the maternal risk of chronic hypertension, obesity, and vascular events. Moreover, individuals born from pregnancies complicated by preeclampsia or fetal growth restriction are at high risk of obesity, diabetes, hypertension, and cardiovascular disease. Therefore, understanding the pathomechanism underlying an increased aIMT in preeclampsia and FGR, as well as subsequent placental dysfunctions, is essential for developing targeted therapies. This review summarizes recent publications regarding IMT and demonstrates how IMT measurements affect predicting perinatal complications.