Journal of Vascular Research最新文献

Introduction: The aim of this study was to determine the effects of atorvastatin on cardiac function and hemodynamics and to investigate its functional mechanism on cardiac fibrosis in acute myocardial infarction (AMI) rats.

Methods: Cardiac functions and hemodynamic changes were evaluated in each group on day 28. Quantitative reverse transcription-polymerase chain reaction, Western blot, and immunohistochemistry were performed to detect the expression of notch1, transforming growth factor-β (TGF-β), Smad2, Smad7, as well as myocardial fibrosis factors (i.e., collagen I, collagen III, and galectin-3) in the myocardial tissues of AMI rats. The changes of myocardial cell structure and myocardial collagen fibers of AMI rats were observed with hematoxylin and eosin staining and Masson staining.

Results: Atorvastatin improved the cardiac function and hemodynamic performance. Atorvastatin downregulated the expression of notch1, smad2, collagen I, and collagen III in AMI rats. Atorvastatin treatment decreased the transcription of notch1, TGF-β, and smad2, while it increased smad7 in AMI rats. Atorvastatin induced the downregulation of collagen I, collagen III, and galectin-3. Myocardial immunohistochemical analysis showed atorvastatin inhibited the expression of notch1, TGF-β, and smad2 in myocardial tissues.

Conclusion: Atorvastatin inhibited myocardial fibrosis by interfering with notch1-TGF-β-smads signal pathways. In addition, it could mitigate myocardial remodeling and improve cardiac functions and hemodynamics.

Introduction: Control of blood pressure following acute type B aortic dissection usually requires sympatholytic antihypertensive medication. Although sympathetic nerve activity is central to blood pressure control, its role in the hypertensive response to acute aortic dissection has not been assessed.

Methods: A prospective pilot study was performed over an 18-month period. Patients presenting with acute type B aortic dissection confirmed on computed tomographic angiography were recruited. We measured blood pressure, heart rate, muscle sympathetic nerve activity (MSNA), and plasma catecholamine levels in patients following acute type B dissection and controls. Comparisons between groups were made 1 week (acute phase) and 3 months after dissection (recovery phase).

Results: Five patients and four controls were recruited in the study. MSNA was higher in patients than controls during the acute phase of aortic dissection: 62 (60-62) versus 46 (29-60) bursts/min (effect size 0.88) and 88 (54-96) versus 71 (44-101) bursts/100 beats (effect size 0.60). Plasma normetanephrines were also increased acutely: 821.0 (489.0-884.0) versus 417.0 (348.5-561.5) pmol/L (effect size 0.85).

Conclusion: Sympathetic nerve activity is increased acutely during the first week after type B aortic dissection, resolving towards control values after 3 months. Immediate sympatholytic drug treatment is likely to be crucial in order to prevent the acute and chronic complications of this response. This may confer benefits over and above simply lowering the blood pressure to protect the aorta in the acute phase.

Introduction: Although it is well-known that patients with high bleeding risk (HBR) who undergo percutaneous coronary intervention (PCI) have poor clinical outcomes, the details have not been fully clarified for acute coronary syndrome (ACS) population. The aim of this study was to describe patient and lesion characteristics in patients with ACS and HBR as defined by the Academic Research Consortium (ARC).

Methods: Patients with ACS (n = 961) who underwent optical coherence tomography (OCT)-guided PCI were investigated. They were divided into HBR and non-HBR groups according to the ARC HBR criteria. Clinical background, lesion characteristics on angiography and OCT, and clinical outcomes during the 2-year follow-up period were compared between the groups.

Results: The HBR group comprised 307 patients (32%). The frequency of multi-vessel coronary disease was higher in the HBR group than the non-HBR group (34% vs. 26%, p = 0.015). OCT findings demonstrated a higher frequency of calcified nodules as the underlying pathology for ACS in the HBR group (12% vs. 3%, p < 0.001), with a correspondingly higher frequency of calcified plaques (55% vs. 39%, p < 0.001). Kaplan-Meier estimates of the incidence of major bleeding (11.0% vs. 2.4%, p < 0.001) and cardiac death (8.5% vs. 2.4%, p < 0.001) were more prevalent for the HBR group than the non-HBR group during the follow-up period.

Conclusion: ACS patients with HBR factors had more advanced atherosclerosis which contributed to a higher prevalence of cardiac death as well as major bleeding complications.

Introduction: Stress relaxation is considered a property of smooth muscle. Rings of thoracic aorta with/without perivascular adipose tissue (PVAT) stress relax. However, rings of isolated PVAT, containing no organized smooth muscle, also stress relax. We hypothesize that smooth muscle is not necessary in the individual tunicas of the aorta for stress relaxation to occur.

Methods: Histochemical staining and isometric contractility were performed on whole or tunicas of the thoracic aorta from the male and female Dahl salt-sensitive rats on normal diet. Masson trichrome and Verhoeff Van Gieson staining validated the isolation of the different tunicas. Stress relaxation was measured after cumulative amounts of passive tension were applied in the presence or absence of extracellular Ca2+, followed by challenge with the a1 adrenergic agonist phenylephrine (PE, 10-5 M).

Results: Stress relaxation occurred in all tunicas at each passive tension regardless of Ca2+. PE-induced contraction was observed in tissues containing smooth muscle (media, whole vessel) but not in the adventitia and aPVAT with Ca2+. No contraction was observed with no Ca2+.

Conclusions: All tunicas of the rat thoracic aorta stress relax, doing so without dependence on smooth muscle or Ca2+. PVAT demonstrated the greatest ability to stress relax.

Introduction: Endogenous biological timing mechanisms are fundamental aspects of living cells, tissues, and organisms. Virtually every aspect of physiology and behavior is mediated by self-sustaining circadian clocks, which depend on light to synchronize with the external daily environment. However, exposure to artificial light at night (ALAN) can impair temporal adaptations and affect health and disease.

Methods: During a study of the effects of long-term ALAN exposure on cardiovascular function, we serendipitously detected ultradian rhythms in muscarinic receptor dependent relaxation of isolated aortic tissue.

Results and conclusion: Mice exposed to dark nights displayed an ultradian pattern of maximum endothelial-dependent relaxation that was antiphase between the sexes. Rhythmic patterns of relaxation were abolished by ALAN exposure in both sexes suggesting that ALAN exposure can affect ultradian rhythms in physiology and behavior.

Introduction: QSOX1, a sulfhydryl oxidase involved in arterial remodelling, has recently emerged as a biomarker for preeclampsia and acute heart failure. This study sought the cardiovascular roles of Qsox1 in response to angiotensin II (AngII)-induced hypertension.

Methods: With approval from an Animal Ethics Committee (CNREEA#9), two models were developed: Qsox1-invalidated adult male mice (Qsox1-/-) mice (C57BL/6J background) and a tamoxifen-inducible, vascular smooth muscle cell (VSMC)-specific Qsox1 knockout. Hypertension was induced via AngII minipumps and trans-aortic constriction, with assessments of cardiac function, vessel size, and VSMC phenotype.

Results: Qsox1-/- at baseline had lower blood pressure and exhibited a synthetic/immature VSMC phenotype in coronary arteries when compared to wild-type (WT). After 4 weeks of AngII infusion, Qsox1-/- mice showed acute heart failure, absent coronary media hypertrophy, and increased perivascular fibrosis compared to hypertensive WT controls (p < 0.01). VSMC-specific Qsox1 knockout leading to the lack of Qsox1 in VSMC only impairs the phenotype of these cells without effecting cardiac function in response to AngII.

Conclusion: These data implicate vascular Qsox1 in the adaptive mechanisms of VSMC to pressure overload such as the development of media hypertrophy.

Introduction: Heart failure with preserved ejection fraction (HFpEF) is a common syndrome with high morbidity and mortality but without available evidence-based therapies. It is essential to investigate changes in gene expression profiles in preclinical HFpEF animal models, with the aim of searching for novel therapeutic targets.

Methods: Wild-type male C57BL/6J mice were administrated with a combination of high-fat diet (HFD) and inhibition of constitutive nitric oxide synthase using N-nitro-l-arginine methyl ester (l-NAME) for 5 and 7 weeks. RNA sequencing was conducted to detect gene expression profiles, and bioinformatic analysis was performed to identify the core genes, pathways, and biological processes involved.

Results: A total of 1,347 genes were differentially expressed in the heart at week 5 and 7 post-intervention. Gene Ontology enrichment analysis indicated that these greatly changed genes were involved mainly in cell adhesion, neutrophil chemotaxis, cell communication, and other functions. Using hierarchical cluster analysis, these differentially expressed genes were classified into 16 profiles. Of these, three significant profiles were ultimately identified. Gene co-expression network analysis suggested troponin T type 1 (Tnnt1) directly regulated 31 neighboring genes and was considered to be at the core of the associated gene network.

Conclusion: The combined application of RNA sequencing, hierarchical cluster analysis, and gene network analysis identified Tnnt1 as the most important gene in the development of HFpEF.

Introduction: It is well documented that high-salt (HS) diet increases systemic and vascular oxidative stress in various animal models and in humans, leading to impairment of vascular reactivity. The present study examined the interaction of genotype and HS diet intake and the potential effects of oxidative stress - antioxidative system balance on the flow-induced dilation (FID) in pressurized carotid arteries of normotensive Tff3-/-/C57BL/6N knockout mice and their wild-type (WT) controls.

Methods: Male, ten-week-old transgenic Tff3-/-/C57BL/6N (Tff3-/-) knockout mice and WT/C57BL/6N (WT) (parental strain) healthy mice were divided in LS (0.4% NaCl in rodent chow) and HS (4% NaCl in rodent chow fed for 1 week) groups. Additionally, LS and HS groups were treated with 1 mmol/L 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPOL) dissolved in the drinking water. After anesthesia with ketamine chloride (100 mg/kg) and midazolam (5 mg/kg), blood pressure was measured, carotid arteries and aortas were isolated, and blood samples were collected.

Results: FID was decreased in WT_HS mice and restored by superoxide scavenger TEMPOL in vivo. On the other hand, attenuated FID of Tff3-/- mice was not further affected by HS diet or TEMPOL in vivo treatment. Vascular superoxide/reactive oxygen species levels were increased with HS diet in both strains and restored by TEMPOL. HS upregulated glutathione peroxidase 1 (GPx1) gene expression in WT_HS and Tff3-/-_HS mice, while GPx activity was significantly decreased only in WT_HS group. Systemic (serum) markers of oxidative stress (oxLDL and AOPP) and arterial blood pressure were similar among groups.

Conclusion: HS diet increases vascular oxidative stress and impairs vasodilation in WT mice. Tff3 gene deficiency attenuates vasodilation per se, without further effects of HS intake. This can be attributed to vascular upregulation of antioxidative enzyme GPx1 in Tff3-/-/C57BL/6N mice conferring protection from oxidative stress.