Journal of Vascular Research最新文献

Introduction: This study evaluated the repeatability of a heating and pressure protocol using laser Doppler flowmetry to measure the full dynamic range of skin microvascular responses at the sacrum and heel - key sites for pressure injury risk.

Methods: Twelve healthy participants (10 male, 2 female; mean age 28 ± 4 years; stature 1.77 ± 0.11 m; body mass 72.6 ± 11.9 kg; body mass index 23 ± 3 kg/m²) completed sacrum assessments. Eleven participants (9 male, 2 female; mean age 28 ± 4 years; stature 1.77 ± 0.57 m; body mass 79.5 ± 9.8 kg; body mass index 20.4 ± 4.5 kg/m²) completed heel assessments. Each participant underwent three identical experimental sessions comprising four phases: baseline, local heating, loading, and pressure release. Skin blood flow was measured continuously. Repeatability was assessed using intraclass correlation coefficients (ICC), with an ICC of 0.75 as a minimum threshold for acceptable repeatability. Four methods were tested to identify the pressure at which blood flow ceased: segmental regression, visual analysis of the initial plateau in blood flow, visual analysis of the final cessation of blood flow, and the plateau that corresponds the final-minute mean.

Results: The protocol showed good to excellent repeatability for baseline flow, settled flow at 42°C, and post direct-pressure reactive hyperaemia. Maximum combined thermal and reactive hyperaemia demonstrated excellent repeatability at the sacrum (ICC = 0.93) and heel (ICC = 0.91), while the area under the curve showed good repeatability at the sacrum (ICC = 0.81) and excellent at the heel (ICC = 0.90). Segmental regression showed the strongest repeatability (ICC = 0.90 at the sacrum; ICC = 0.84 at the heel). Visual inspection of the initial plateau in blood flow and absolute cessation of blood flow also exceeded the threshold for acceptable repeatability.

Conclusion: This study presents a reproducible protocol for assessing pressure-induced microvascular compromise, capturing responses from complete vascular occlusion to peak thermal-pressure hyperaemic vasodilation. Applied at the sacrum and heel, it offers a quantifiable, non-invasive tool to investigate pressure injury risk in vulnerable populations. It also supports future evaluations of support surfaces, offloading strategies, and novel therapeutic interventions to improve tissue pressure tolerance.

Introduction: Precise visualization of digital artery perforators (DAPs) is essential for anatomical research and microsurgical planning. Traditional injection techniques often fail to highlight small-calibre vessels and pose technical or environmental limitations. Gelatine is biocompatible and easy to use, and methylene blue provides strong contrast. However, no prior studies have combined both for vascular enhancement.

Methods: Twenty digits from five fresh-frozen cadaveric upper limbs (mean age: 83 years, all female) were used. After saline irrigation, radial and ulnar arteries were perfused with 24 g/L gelatine and 1% w/v methylene blue via 18G cannulas. Limbs were warmed to enhance dye flow, then chilled overnight. Digits were dissected to expose DAPs. Kruskal-Wallis tests confirmed consistent perfusion and high inter- and intra-observer reliability (P ≥ 0.81).

Conclusion: This gelatine-methylene blue technique provides a reliable, cost-effective method for clear and reproducible vascular visualization in cadaveric studies and surgical training.

Objective: To elucidate gene expression changes associated with different stages of calcification in carotid artery plaques and clarify the dynamic biological processes underlying plaque maturation.

Methods: Carotid plaque specimens were classified into four groups-mildly, moderately, severely, and very severely calcified-based on calcium scores derived from computed tomography. RNA-Seq (SMART-Seq) analysis and qRT-PCR validation were performed to assess expression profiles of genes related to vascular smooth muscle cell (VSMC) phenotype, inflammation, extracellular matrix (ECM), and calcification.

Results: Mildly calcified plaques exhibited elevated inflammatory (CD68, TNF) and osteogenic (RUNX2, SPP1/OPN) gene expression. Moderately calcified plaques showed transient suppression of these genes with upregulation of ELN, suggesting structural stabilization. In severely calcified plaques, osteogenic and inflammatory gene expression persisted, while contractile markers (ACTA2, MYH11) showed limited reactivation. Very severely calcified plaques demonstrated downregulation of VSMC-related genes and selective ECM remodeling, indicating a quiescent, structurally stabilized stage.

Conclusion: Carotid plaque calcification represents a dynamic, multistage process characterized by reversible and irreversible transitions in VSMC phenotype and ECM composition. These findings emphasize that calcification is not merely passive deposition but reflects coordinated cellular and molecular remodeling, which may inform future stage-specific therapeutic strategies.

Background: Blood-brain barrier (BBB) dysfunction has been associated with vascular dementia (VaD). However, the underlying mechanisms causing BBB dysfunction remain unclear, especially regarding cerebral hypoperfusion. This study aims to investigate the effects of asymmetric hypoperfusion on BBB permeability using a mouse model of VaD.

Methods: Asymmetric bilateral carotid artery stenosis (ACAS) was induced using ligature rings. BBB integrity was assessed on 3 days post-surgery using Evans blue, IgG and albumin extravasation. A modified tissue processing protocol optimized endogenous markers detection. Regional and sex-based differences in BBB permeability were analyzed.

Results: Increased BBB permeability was observed in both corpus callosum and cortical areas, with significantly more severe leakage in the left cortex compared to the right, correlating directly with lower cerebral blood flow on the left side. In contrast, no significant asymmetrical difference in BBB permeability was detected in the corpus callosum. Additionally, male and female mice exhibited similar patterns of BBB permeability.

Conclusion: This study provides the first evidence that asymmetrical hypoperfusion significantly impacts regional BBB permeability in a mouse model of VaD. These findings highlight the importance of local hemodynamic changes in driving BBB dysfunction and underscore potential therapeutic targets for preventing or mitigating vascular dementia progression.

Introduction: We describe methods by which vasomotion can be recorded in awake and anesthetized human subjects without significant interference from other spontaneous vascular oscillations.

Methods: In three separate studies, we used photoplethysmography (PPG) to record vasomotion in fingertips. In Study 1, we induced chemical sympathectomy in the studied hand of 11 awake subjects who received intravenous dexmedetomidine infusions. In Study 2, we administered four progressively increasing intravenous dexmedetomidine infusions to 16 awake volunteers. In Study 3, we recorded vasomotion simultaneously from 6 fingers of 7 patients who were under dexmedetomidine-based anesthesia. Five-minute epochs of PPG recordings that displayed slow vascular oscillations were analyzed for frequency and amplitude.

Results: In Study 1, vasomotion frequencies were 0.025 ± 0.008 Hz. In Study 2, vasomotion frequencies were 0.033 ± 0.006 Hz, and 0.032 ± 0.008 Hz during the two highest dexmedetomidine infusion steps. In Study 3, vasomotion frequencies ranged from 0.020 to 0.037 Hz and were observed in all 6 fingers, with no synchrony between the six fingers.

Conclusion: The vascular oscillations we observed without significant interference from other spontaneous oscillations are independent of neural activity (Study 1), local in nature (Study 3), and associated with alpha-2-adrenoceptor activation, consistent with known properties of vasomotion.

Introduction: Inflammatory pathways in vascular disease are the focus of intense interest. Multiple studies have shown that interleukin-6 (IL-6) is strongly implicated in the atherosclerotic process. Accumulating evidence suggests a similar role for growth differentiation factor-15 (GDF-15).

Methods: In this study, we measured and compared circulating levels of IL-6 and GDF-15 in a cohort of 20 vascular surgical patients with atherosclerotic disease presenting for surgical revascularization (carotid endarterectomy or common femoral artery endarterectomy) and in a similar number of age-matched healthy volunteers. A cross-sectional analysis of prospectively collected data was performed, with serum GDF-15 and IL-6 levels measured and assessed using enzyme-linked immunosorbent assays (ELISAs).

Results: We observed substantial circulating levels of GDF-15 in most patients (17/20) compared to the reference range upper limit of 1,500 pg/mL, irrespective of the type of vascular disease and revascularization procedure they were undergoing. In contrast, only 1 healthy control participant had a borderline high GDF-15 of 1,572 pg/mL. Indeed, the mean serum GDF-15 level between patients (2,515 pg/mL, SD 906) and healthy controls (1,016 pg/mL, SD 219) was highly significant (p value <0.001). On the other hand, although IL-6 levels between patients (mean 3.6, SD 2.54 pg/mL) and healthy controls (mean 2.2, SD 0.67 pg/mL) were significantly different (p = 0.020), only 7 patients had values above the reference range upper limit of 3.4 pg/mL.

Conclusion: These results suggest that serum GDF-15, but not IL-6, is a strong candidate for use as a biomarker of atherosclerotic vascular disease and may allow for earlier risk factor modification to help prevent disease onset and progression. Large-scale studies aimed at determining whether a rising GDF-15 is an indication of worsening outcome in a wider spectrum of patients with vascular disease are clearly warranted.

Introduction: In our study, the possible role of the calcium-sensing receptor (CaSR) pathway in L-cysteine-/hydrogen sulfide (H₂S)-induced vasorelaxations was investigated in isolated mouse thoracic aorta tissue.

Methods: For this purpose, vasorelaxations to L-cysteine (H₂S substrate; 1 µm-10 mm) and calindol (CaSR agonist; 0.3-10 μm) were measured in endothelial-intact and -denuded thoracic aorta segments contracted with phenylephrine (5 μm). Also, the effects of propargylglycine (PAG) and Calhex-231, cystathionine-gamma-lyase (CSE) and CaSR inhibitor, respectively, on L-cysteine- and calindol-induced vasorelaxations were investigated in thoracic aorta segments. In addition, the effects of L-cysteine, calindol, and endothelium on H₂S generation in mouse aorta segments were investigated.

Results: L-cysteine- and calindol-induced vasorelaxations were reduced in the presence of PAG and Calhex-231. Furthermore, in endothelium-denuded tissues, the vasorelaxations to calindol and L-cysteine were reduced compared to endothelium-intact tissues. Also, calindol increased basal H₂S generation, and PAG and Calhex-231 reduced the increase in H₂S production stimulated with calindol. Calhex-231 reduced the increase in H₂S production in the presence of L-cysteine. Also, H₂S production decreased in endothelium-denuded tissues.

Conclusion: Endogenous H₂S generated by CSE produces endothelium-dependent relaxation by activating CaSR in mouse thoracic aorta tissue.

Introduction: Immunosuppressive medications are widely used to treat patients with neoplasms, autoimmune conditions, and solid organ transplants. Prior studies indicate that immunosuppression drugs can cause adverse vascular remodeling. Given the systemic effects of the drugs, elucidating cell-type-specific drug effects has been challenging.

Methods: We utilized induced pluripotent stem cell-derived endothelial cells to investigate the role of widely used immunosuppression drugs on endothelial cell function.

Results: We found that among immunosuppression agents, sirolimus reduced basic endothelial cell functions including cell migration, proliferation, acetylated LDL uptake, mitochondrial respiration, and angiogenic properties, while tacrolimus only reduced nitric oxide release.

Conclusions: This model allows for investigation of differential effect of immunosuppression drugs on endothelial function that can elucidate the mechanisms contributing to clinically observed adverse vascular profiles.

Introduction: Abdominal aortic aneurysm (AAA) is a multifactorial disease with limited identification of contributing genetic factors. p27kip, also known as CDKN1B, is a cell cycle inhibitor that regulates vascular smooth muscle cells (VSMCs) and macrophages (Mϕ). The role of p27 in AAA development was assessed by AAA induction in p27 knockout (p27-/-) and wild-type (WT) mice.

Methods: AAAs were induced in male and female p27-/- and WT mice via topical elastase with oral administration of 3-aminopropionitrile fumarate salt. Aortic diameter was measured with ultrasound. VSMCs and macrophages were quantified by immunohistochemistry. Oxidative stress genes were analyzed using polymerase chain reaction. In vitro cell proliferation, migration, and oxidative stress assay were performed on VSMCs isolated from abdominal aortas.

Results: p27-/- mice developed significantly larger AAA diameter than WT mice with reduced VSMCs and increased macrophages. M1ϕ were significantly elevated in p27-/- mice, while M2ϕ were more abundant in WT mice. p27-/- mice had lower expression of the antioxidant gene, Nrf2. In vitro experiments demonstrated increased proliferation and migration in p27-/- cells with increased oxidative stress sensitivity.

Conclusion: Knockout of p27 accelerated aneurysm growth with increased macrophage infiltration, VSMC loss, and decreased antioxidant factors, highlighting a potential role for p27 in AAA progression.

Introduction: Given the lack of effective pharmacotherapy for vascular dementia (VaD) and the reported benefits of exercise, this study examined the impact of water temperature during aquatic exercise (AE) on cognitive and pathological outcomes in a mouse model of VaD.

Methods: Twelve-month-old male mice underwent bilateral common carotid artery stenosis (BCAS) to induce chronic cerebral hypoperfusion. Groups included sham, BCAS control (no exercise), and BCAS mice assigned to AE in water baths at 25°C, 30°C, or 35°C. Cognitive performance was assessed using the elevated plus maze, Y-maze, and novel object recognition test (NORT). Brain tissues were analyzed for microglial marker CD68, astrocytic marker GFAP, and myelin basic protein (MBP) in the corpus callosum.

Results: The 30°C AE group showed the greatest improvement in NORT performance and swim activity. CD68 expression was unchanged across groups, but GFAP expression was significantly reduced at 30°C, suggesting suppressed astrocyte activation. Furthermore, the decline in MBP expression after BCAS was attenuated in this group, indicating preserved white matter integrity.

Conclusion: AE at approximately 30°C alleviated cognitive deficits in a VaD model, likely by reducing neuroinflammation and protecting myelin. These findings highlight the therapeutic potential of optimizing AE conditions, particularly water temperature, for dementia-related rehabilitation.