Search Results (37)

Hydrolyzed collagen (HC) derived from salmon skin is a promising source of bioactive peptides. In this study, the vasorelaxant effects and potential mechanisms of action of HC on isolated rat thoracic aorta rings were investigated using the organ bath technique. The vasorelaxant properties of HC were evaluated using aortic rings from Wistar rats pre-contracted with phenylephrine (PE) or potassium chloride (KCl). HC induced significant vasorelaxation in both endothelium-intact and endothelium-denuded rings, indicating that its mechanism of action was independent of the endothelium and involved direct effects on vascular smooth muscle cells. The vasorelaxant effect of HC was reduced when pre-contraction was induced by tetraethylammonium chloride (TEA). However, the vasodilatory effects of HC were not significantly inhibited by all K⁺ channel blockers, including glibenclamide, barium chloride (BaCl₂), or 4-aminopyridine (4-AP). Additionally, pre-incubation with prazosin, an α-adrenoceptor blocker, significantly reduced the vasorelaxation induced by HC, whereas propranolol, a β-adrenoceptor blocker, had no effect. In addition, HC inhibited CaCl₂-induced contractions induced by both PE and caffeine in a Ca²⁺-free solution. Therefore, HC exhibited the vasorelaxant effects through an endothelium-independent mechanism. The vasodilatory effects of HC were associated with the activation of K_Ca channels, suppression of PE-induced contraction via α₁-adrenergic receptor pathways, and inhibition of CaCl₂-induced contractions by modulating intracellular Ca²⁺ release and extracellular Ca²⁺ influx in vascular cells. Full article

Background: Atherosclerosis forms the background of several cardiovascular pathologies. LDL receptor knockout (LDLR-KO) mice kept on a high-fat diet (HFD) develop high cholesterol levels. Previously we found that vasodilation responses in HFD LDLR-KO mice were improved in the absence of type 1 cannabinoid receptors (CB₁Rs). We aimed to reveal the effects of HFD and CB₁Rs on vascular contractile and structural properties. Methods: Experiments were performed on LDLR-CB₁R double knockout and wild type (WT) mice, kept on an HFD or control diet (CD) for 5 months. Thoracic aortas were isolated for Oil Red plaque staining and abdominal aorta segments for myography to obtain phenylephrine (Phe)-induced (100 nM–10 µM) contractile responses. Aorta samples were subjected to histology stainings with hematoxylin–eosin and resorcin–fuchsin (elastin density) and for smooth muscle actin (SMA) immunohistochemistry. Results: Phe-induced contractions significantly increased in HFD groups (p < 0.05) similarly in all genotypes. However, contractions were stronger with CD in CB₁R-KO compared to WT. Plaque areas were increased in LDLR-KO mice compared to WT, significant in HFD groups (p < 0.05). SMA increased to HFD, while elastin density remained similar, with the highest value in double KO-HFD. Intima/media ratio significantly decreased in double KO-HFD vs. CD. Conclusions: Our results indicate that HFD-treated LDLR-KO mice develop atherosclerosis with functional contractile and structural alterations modulated by CB₁Rs: absence of CB₁Rs elicited higher contraction properties with some modification in vascular remodeling indicating contribution of the CB₁R to cellular signalization controlling wall thickness and elasticity in pathological conditions. Full article

Berries are an excellent source of bioactive compounds, particularly polyphenols, and have been widely used in folk medicine by the Mapuche people of southern Chile. In this study, a hydroalcoholic extract of Berberis congestiflora Gay (BE) was analyzed to determine its phytochemical composition and to evaluate its antioxidant capacity, vasorelaxant effects in rat aortas, and inhibitory activity on enzymes related to chronic non-communicable diseases, including exploration of a possible vasodilatory mechanism in isolated rat aortas. Antioxidant activity was assessed using Oxygen Radical Absorbance Capacity (ORAC), DPPH (2,2-diphenyl-1-picrylhydrazyl), and ABTS (2,2-azinobis-(3-ethylbenzothiazolin-6-sulfonic acid)) radical scavenging assays, as well as ferric reducing antioxidant power (FRAP). Vascular responses to the Berberis extract were studied using isometric tension recordings in an ex vivo rat thoracic aortic ring model, and the chemical constituents of BE were identified for the first time by HPLC-DAD-MS. The extract itself produced a dose-dependent contraction at 100 and 1000 µg/mL and induced relaxation in phenylephrine-precontracted aortas at the same concentrations, with a maximum contraction of 71% and maximum relaxation of 70% at 1000 µg/mL. Mechanistically, the extract triggered calcium-mediated contraction primarily through calcium release from the sarcoplasmic reticulum and, to a lesser degree, via extracellular Ca²⁺ influx, while its relaxant effect depended on an intact endothelium and activation of the NO/cGMP pathway. In addition, the extract showed inhibitory activity against cholinesterase, glucosidase, and amylase, with IC₅₀ values of 7.33 ± 0.32, 243.23 ± 0.3, and 27.21 ± 0.03 µg/mL, respectively, and docking studies were carried out for selected berry compounds. Overall, these findings indicate that these berries are a rich source of bioactive constituents with antioxidant properties and endothelium-dependent vasodilator effects, supporting their traditional use and highlighting their potential as enzyme inhibitors and as promising candidates for the development of phytotherapeutic products, particularly as supplements for chronic disease management. Full article

Vascular function is a direct factor affecting blood pressure, and it is a primary strategy for clinically controlling hypertension by regulating the constriction/relaxation of blood vessels. This study evaluates the vasodilatory and anti-hypertensive effects of norisoboldine (NOR), an isoquinoline alkaloid in Ayurvedic medicine. The rat thoracic aorta was isolated to investigate the vasodilatory effect, and L-NAME-induced hypertensive rats were established, respectively. In the isolated vascular ring, removal of the endothelium resulted in a significant decrease in the vasodilatory effect. Pretreatment with L-NAME, ODQ, KT5823, WT, Tri, Dilt, calcium-free solution, TG, Gd³⁺, 2-APB, Indo, 4-AP, Gli, and BaCl₂ inhibited the vasodilatory effect of NOR. In vascular endothelial cells, NOR promoted eNOS phosphorylation and inhibited TNF-α-induced expression of ICAM-1 and VCAM-1. SBP and DBP were significantly decreased after administration of different doses of NOR in the femoral vein of rats. In addition, NOR significantly reduced the blood pressure of L-NAME-induced hypertensive rats, up-regulated the serum levels of NO, cGMP, and CAT, and down-regulated MDA, IL-6, and TNF-α in hypertensive rats. NOR administration improved pathological changes in the thoracic aorta by regulating the arrangement of thoracic aortic smooth muscle cells, decreasing the thickness of the thoracic aortic wall, and reducing the degree of collagen deposition and fibrosis. In conclusion, the vasodilatory mechanisms of NOR were related to the Ca²⁺-eNOS signaling pathway, including the PGI₂ and various K⁺/Ca²⁺ channels, the inositol triphosphate receptor (IP₃R) calcium release, and the α-adrenergic receptor pathway. The anti-hypertensive mechanism of NOR may be related to increased NO and cGMP bioavailability, inhibition of oxidative stress and inflammatory responses, and improved vascular remodeling. Full article

Background: Hypertension and its complications are a major global health problem, and natural compounds with vasorelaxant effects are being investigated as potential antihypertensive agents. Objective: This study aimed to determine whether rosmarinic acid (RA) induces vasorelaxation in the rat thoracic aorta and to elucidate the underlying mechanisms. Methods: Isolated thoracic aortic rings, with or without endothelium, were precontracted with phenylephrine and subsequently exposed to cumulative concentrations of RA. The roles of endothelium-derived factors, potassium channels, and calcium signaling were evaluated using selective pharmacological inhibitors and activators. In addition, the involvement of the AMPK pathway, adenylate cyclase/cAMP pathway, PKC signaling, β-adrenergic receptors, muscarinic receptors, and angiotensin II in RA-induced vasorelaxation was investigated. Results: RA induced a concentration-dependent vasorelaxation in endothelium-intact thoracic aortic rings (p < 0.001; pD₂ = 7.67 ± 0.04). The vasorelaxant effect of RA was attenuated in endothelium-denuded vessels (pD2: 5.26 ± 0.18). The relaxation response was significantly attenuated by inhibitors of the PI3K/Akt/eNOS/NO/cGMP pathway and by blockers of BK_Ca, IK_Ca, and Kv potassium channels (p < 0.001). Furthermore, RA markedly inhibited both extracellular Ca²⁺ influx and intracellular Ca²⁺ release from the sarcoplasmic reticulum (p < 0.001). RA incubation also significantly reduced the contractions induced by angiotensin II (Ang II) and by the PKC activator PMA (p < 0.001). Other tested pathways had no significant influence on the vasorelaxant effect of RA (p > 0.05). Conclusions: These findings demonstrate that rosmarinic acid induces both endothelium-dependent and endothelium-independent vasorelaxation in the rat thoracic aorta through activation of the PI3K/Akt/eNOS/NO/cGMP pathway, opening of BK_Ca, IK_Ca, and Kv potassium channels, and suppression of Ca²⁺ mobilization. Additionally, inhibition of PKC- and angiotensin II-mediated vascular contraction contributes to RA-induced vasorelaxation. RA may therefore have therapeutic potential in the management of hypertension. Full article

Endothelial dysfunction is closely linked to inflammation and oxidative stress and ultimately contributes to the development of cardiovascular diseases. Lipopolysaccharide (LPS), a major component of Gram-negative bacteria, induces vascular inflammation and oxidative damage in experimental models. Curcumin (Cur), a polyphenol from Curcuma longa, is well known for its anti-inflammatory and antioxidant properties. In this study, we examined the protective effects of CUD003, a novel synthetic Cur derivative, on the LPS-induced impairment of endothelium-dependent relaxation in the thoracic aorta of mice. Male ICR mice were pretreated with CUD003 or Cur (3 or 10 mg/kg, p.o.) 30 min prior to LPS injection (10 mg/kg, i.p.). Twenty-four hours after LPS injection, vascular reactivity was assessed in isolated aortic rings by evaluating vasorelaxation and vasoconstriction responses. LPS markedly impaired acetylcholine-induced vasorelaxation in the phenylephrine (PE)-precontracted aortic rings, while PE-induced contraction and sodium nitroprusside-induced relaxation were preserved, indicating that LPS impaired endothelium-dependent relaxation without affecting smooth muscle function. Immunohistochemical analysis revealed a reduction in eNOS expression and elevated levels of TNF-α, COX-2, O₂⁻, and malondialdehyde, indicating enhanced inflammation and oxidative stress in the aorta. Pretreatment with CUD003 (10 mg/kg) significantly ameliorated these changes and showed superior protective effects compared to the same dose of Cur. These findings suggest that CUD003 protects against LPS-induced vascular dysfunction and suppresses inflammation and oxidative stress, supporting its potential as a preventive candidate against vascular inflammation and dysfunction. Full article

Background/Objectives: Metabolic syndrome is one of the leading causes of mortality worldwide, with high-fat diet (HFD) intake being a significant driving force. Despite long-term research, new interventions are still being sought to improve cardiovascular disorders associated with metabolic syndrome. Methods: To explore the therapeutic potential of a slow-releasing H₂S donor, we evaluated the effects of 3 weeks of treatment with GYY-4137 on systolic blood pressure (sBP), cardiac parameters, adiposity, selected plasma markers, and the vascular function of the thoracic aortas (TAs) and mesenteric arteries (MAs) isolated from male spontaneously hypertensive rats (SHRs) fed an HFD for 8 weeks. Results: HFD administration induced cardiac remodeling, increased adiposity, and decreased adrenergic contractility in both TAs and MAs. Moreover, although high-fat intake improved TAs relaxation, it decreased aortic protein expression of endothelial NO synthase and the involvement of NO in vasoactive responses of both TAs and MAs. In addition, protein expression of inducible NOS and tumor necrosis factor alpha (TNFα) in aortas was increased, as were plasma levels of chemerin, which has been proposed as a possible link among metabolic and vascular disorders and inflammation. Treatment with GYY-4137 reduced sBP, improved relaxation of the MAs, partially restored the contractility of the TAs, generally restored NO signaling, and decreased the protein expression of the inducible NOS and TNFα, as well as plasma chemerin levels. Conclusions: A slow H₂S-releasing donor could partially ameliorate the metabolic changes induced by increased fat intake during essential hypertension and trigger beneficial vasoactive effects associated with the NO signaling restoration and suppression of inflammation. Full article

Background/Objectives: Patients undergoing open thoracic aortic surgery have the highest bleeding complication rates within cardiac–vascular surgery, but research on coagulation management mostly targets general cardiac surgery. This scoping review evaluates current evidence on intraoperative hemostatic agents and their effect on bleeding and blood transfusions in these patients. Methods: We searched MEDLINE (PubMed), Embase, and Cochrane Library on 2 July 2024. Eligible studies included randomized controlled (RCT) and observational trials with a comparison group and at least a sub-analysis regarding thoracic aortic surgery (excluding thoracoabdominal and isolated descending aorta surgery). Results: Our search yielded 4697 articles, with 33 included. These covered antifibrinolytics (3 RCTs, 10 observational studies), fibrinogen supplementation (3 RCTs, 4 observational studies), recombinant factor VIIa (rFVIIa, 8 observational studies), blood products (3 observational studies), and factor eight inhibitor bypassing activity (FEIBA, 1 RCT, 1 observational study). The impact of blood product transfusion on bleeding control is unclear due to a lack of placebo or no-transfusion comparisons, though it appears associated with more complications. Both FEIBA studies suggest reduced blood product use in aortic dissection surgery—one as rescue therapy, the other as standard treatment. Evidence on fibrinogen supplementation is mixed: a multicenter RCT showed increased transfusions, while smaller RCTs and observational studies showed reductions, possibly due to differences in pretreatment fibrinogen levels and patient selection. Observational studies on rFVIIa show conflicting results, likely due to selection bias. Two small RCTs—one on TXA, one on aprotinin—suggest reduced transfusions and blood loss. Comparative studies of different types of antifibrinolytics yielded conflicting results. Conclusions: Evidence on hemostatic agents in thoracic aortic surgery is limited. Small studies suggest potential for the routine use of antifibrinolytics, FEIBA, and fibrinogen supplementation—but only in bleeding patients with hypofibrinogenemia. High-quality RCTs focused on thoracic aortic procedures are needed to determine optimal coagulation management. Full article

The renin–angiotensin system (RAS) is the main endocrine and tissular component responsible for controlling cardiovascular homeostasis, which can be modulated by estrogen levels. This study investigated the effects of hormone treatments with estrogen and progestins on angiotensin-(1-7)-mediated [Ang-(1-7)] vasodilation in ovariectomized rats and the possible mechanisms involving the RAS. Female Wistar rats were divided into the following groups: sham (SHAM), ovariectomized (OVX), OVX and treated with 17β-estradiol (E2) (OE₂), OVX and treated with E2 and drospirenone (OE₂ + DRSP), and OVX and treated with medroxyprogesterone (MPA). Hormonal treatment was delivered via gavage for 28 days. Vascular responses to Ang-(1-7) were assessed in isolated aortic rings, and a Western blot of the thoracic aorta was used to determine the protein levels of angiotensin II (Ang II) type-1 receptor (AT₁R), Ang II type-2 receptor (AT₂R), Ang-(1-7) receptor (Mas), angiotensin-converting enzyme 2 (ACE2), and endothelial nitric oxide synthase (eNOS). The results showed impaired vascular reactivity caused by ovariectomy. Ang-(1-7) induced vasodilation in the OE₂, OE₂ + DRSP, and MPA-treated groups, while the administration of the AT₂R antagonist (PD123319) or the selective Mas antagonist (A779) increased the extent of vasorelaxation induced by Ang-(1-7) in the OVX + MPA group. There were no differences in the aortic levels of AT₁R or ACE2 between the groups, but the MPA group showed significantly increased levels of AT₂R and eNOS. We concluded that ovariectomy induced vascular dysfunction linked to RAS regulation, and both estrogen (E2) and progestins differentially restored these parameters. Full article

Background/Aim: Rosmarinus officinalis L. (R. officinalis) is an aromatic medicinal species with important nutraceutical potential, having rosmarinic acid (RA) as one of its main metabolites. The present study aims to evaluate the effects of an extract obtained from the leaves of this species and of its main metabolite in improving the streptozotocin-induced damage of hearts and aorta of diabetic rats. Methods: The leaves of the species were used to obtain a hydroethanolic extract, which was analyzed using the LC/MS method. Diabetes mellitus was induced by intraperitoneal streptozotocin administration in rats. After two weeks, oxidative stress parameters were evaluated from the heart and aorta homogenates. NOS3, AMPK, and adiponectin levels were quantified using ELISA tests, and thoracic aorta rings were isolated for contractility evaluation in the organ bath. Phospho-NF-κB, NRF2, HIF1 alfa, iNOS, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) quantification were performed using the Western blot technique. Results: Carnosic acid, together with rosmarinic acid, were proven to be the main metabolites identified in the composition of the tested extract. Administration of the extract and of RA improved the relaxation response to acetylcholine and the redox status, with the reduction in malondialdehyde (MDA), nitric oxide synthase 3 (NOS 3), AMP-activated protein kinase (AMPK), adiponectin, reduced (GSH) and oxidized glutathione (GSSG) levels, and superoxide dismutase (SOD) activity. RA significantly enhanced the expression of HIF 1α, NRF2, and pNFkB in the heart. Conclusions: Administration of the R. officinalis extract and of RA-alleviated oxidative stress, proving vascular and cardiac antioxidant properties in the hearts and aorta of diabetic rats. Full article

Aortitis, defined as inflammation of the aorta, can lead to aneurysms and dissections. Intra-operative sampling is essential for diagnosis, with many cases presenting asymptomatically as clinically isolated aortitis. Previous studies investigating aortitis in major aortic surgery have been limited by low intra-operative sampling. We performed an 11-year, retrospective, cross-sectional study to investigate the true prevalence of aortitis in thoracic aortic aneurysms and dissections by analysing all major aortic operations performed in a single centre. We collected medical histories, histological reports, post-operative outcomes and follow-up data; 537 patients met the inclusion criteria, representing an 88% histological sampling rate. The prevalence of aortitis was 10.6% (n = 57), of which 75% were clinically isolated. The re-operation rate in aortitis was twice that of non-aortitis patients (17.5% vs. 9.4%, p = 0.054). Multivariate logistic regression identified increased age, female sex, current smoking, and other inflammatory diseases as significantly associated with aortitis, with a bicuspid aortic valve associated with a significantly decreased likelihood of aortitis. The true prevalence of aortitis is likely higher than reported in previous studies, with our study showing twice the prevalence found in previous studies with lower sampling rates. Due to the increased re-intervention in aortitis, specialist multi-disciplinary follow-up and aortitis centres should be formed. Full article

Hereditary thoracic aorta diseases (HTADs) are a heterogeneous group of rare disorders whose major manifestation is represented by aneurysm and/or dissection frequently located at the level of the ascending thoracic aorta. The diseases have an insidious evolution and can be encountered as an isolated manifestation or can also be associated with systemic, extra-aortic manifestations (syndromic HTADs). Along with the development of molecular testing technologies, important progress has been made in deciphering the heterogeneous etiology of HTADs. The aim of this study is to identify the genetic variants associated with a group of patients who presented clinical signs suggestive of a syndromic form of HTAD. Genetic testing based on next-generation sequencing (NGS) technology was performed using a gene panel (Illumina TruSight Cardio Sequencing Panel) or whole exome sequencing (WES). In the majority of cases (8/10), de novo mutations in the FBN1 gene were detected and correlated with the Marfan syndrome phenotype. In another case, a known mutation in the TGFBR2 gene associated with Loeys–Dietz syndrome was detected. Two other pathogenic heterozygous variants (one de novo and the other a known mutation) in the SLC2A10 gene (compound heterozygous genotype) were identified in a patient diagnosed with arterial tortuosity syndrome (ATORS). We presented the genotype–phenotype correlations, especially related to the clinical evolution, highlighting the particularities of each patient in a family context. We also emphasized the importance of genetic testing and patient monitoring to avoid acute aortic events. Full article

High systolic blood pressure and increased blood pressure variability after the onset of ischemic stroke are associated with poor clinical outcomes. One of the key determinants of blood pressure is arteriolar size, determined by vascular smooth muscle tone and vasodilatory and vasoconstrictor substances that are released by the endothelium. The aim of this study is to outline alterations in vasomotor function in isolated peripheral arteries following ischemic stroke. The reactivity of thoracic aortic segments from male C57BL/6 mice to dilators and constrictors was quantified using wire myography. Acetylcholine-induced endothelium-dependent vasodilation was impaired after ischemic stroke (LogIC50 Sham = −7.499, LogIC50 Stroke = −7.350, p = 0.0132, n = 19, 31 respectively). The vasodilatory responses to SNP were identical in the isolated aortas in the sham and stroke groups. Phenylephrine-induced vasoconstriction was impaired in the aortas isolated from the stroke animals in comparison to their sham treatment counterparts (Sham LogEC50= −6.652 vs. Stroke LogEC50 = −6.475, p < 0.001). Our study demonstrates that 24 h post-ischemic stroke, peripheral vascular responses are impaired in remote arteries. The aortas from the stroke animals exhibited reduced vasoconstrictor and endothelium-dependent vasodilator responses, while the endothelium-independent vasodilatory responses were preserved. Since both the vasodilatory and vasoconstrictor responses of peripheral arteries are impaired following ischemic stroke, our findings might explain increased blood pressure variability following ischemic stroke. Full article

Background: The aim of this study is to define and determine the rate of acute non-A–non-B aortic dissections, and to evaluate CT angiography findings and possible complications, as well as to discuss management strategies and currently available therapy. Non-A non-B type of aortic dissection is still a grey area in the radiologist’s mind, such that it is not entirely clear what should be reported and completed in terms of this disease. Methods: A retrospective single-center study including 36 pre-treatment CT angiograms of consecutive patients (mean age: 61 years) between January 2012 and December 2022 with aortic dissection involving the aortic arch with/without the thoracic descending/abdominal aorta (type non-A non-B). Results: According to the dissection anatomy, we identified three modalities of spontaneous acute non-A–non-B anatomical configurations. Configuration 1 (n = 25) with descending-entry tear and retrograde arch extension (DTA entry). Configuration 2 (n = 4) with Arch entry tear and isolated arch involvement (Arch alone). Configuration 3 (n = 7) with Arch entry and anterograde descending (±abdominal) aorta involvement (Arch entry). CT angiogram findings, management, and treatment options are described. Conclusions: Acute non-A non-B dissection represents an infrequent occurrence of aortic arch dissection (with or without involvement of the descending aorta) that does not extend to the ascending aorta. The complete understanding of its natural progression, distinct CT angiography subtypes, optimal management, and treatment strategies remains incomplete. Within our series, patients frequently exhibit a complex clinical course, often necessitating a more assertive approach to treatment compared to type B dissections. Full article

Background: We sought to investigate magnetic resonance imaging (MRI) parameters that correspond to vasculitis observed via [¹⁸F]FDG positron emission tomography/computed tomography (PET/CT) and ultrasound in patients with large-vessel giant cell arteritis (LV-GCA). Methods: We performed a cross-sectional analysis of patients diagnosed with LV-GCA. Patients were selected if MRI, PET/CT, and vascular ultrasound were performed at the time of LV-GCA diagnosis. Imaging findings in vessel segments (axillary segment per side, thoracic aorta) assessed using at least two methods were compared. Vessel wall thickening, oedema, and contrast agent enhancement were each assessed via MRI. Results: Twelve patients with newly diagnosed LV-GCA were included (seven females, 58%; median age 72.1, IQR 65.5–74.2 years). The MRI results showed mural thickening in 9/24 axillary artery segments. All but 1 segment showed concomitant oedema, and additional contrast enhancement was found in 3/9 segments. In total, 8 of these 9 segments corresponded to vasculitic findings in the respective segments as observed via PET/CT, and 2/9 corresponded to vasculitis in the respective ultrasound images. If MRI was performed more than 6 days after starting prednisone treatment, thickening and oedema were seen in only 1/24 segments, which was also pathologic according to ultrasound findings but not those obtained via PET/CT. Four patients had mural thickening, oedema, and contrast enhancement in the aorta, among whom three patients also had vasculitic findings observed via PET/CT. Isolated mural thickening in one patient corresponded to a negative PET/CT result. Conclusions: In the MRI results, mural thickening due to oedema corresponded to vasculitic PET/CT findings but not vasculitic ultrasound findings. The duration of steroid treatment may reduce the sensitivity of MRI. Full article