Vascular-related Diseases Research Articles

A microvascular image analysis method for optical-resolution photoacoustic microscopy

Optical-resolution photoacoustic microscopy (OR-PAM) has been shown to be an excellent tool for high-resolution imaging of microvasculature, and quantitative analysis of the microvasculature can provide valuable information for the early diagnosis and treatment of various vascular-related diseases. In order to address the characteristics of weak signals, discontinuity and small diameters in photoacoustic microvascular images, we propose a method adaptive to the microvascular segmentation in photoacoustic images, including Hessian matrix enhancement and the morphological connection operators. The accuracy of our vascular segmentation method is quantitatively evaluated by the multiple criteria. To obtain more precise and continuous microvascular skeletons, an improved skeleton extraction framework based on the multistencil fast marching (MSFM) method is developed. We carried out in vivo OR-PAM microvascular imaging in mouse ears and subcutaneous hepatoma tumor model to verify the correctness and superiority of our proposed method. Compared with the previous methods, our proposed method can extract the microvascular network more completely, continuously and accurately, and provide an effective solution for the quantitative analysis of photoacoustic microvascular images with many small branches.

Endothelial Ca2+ signaling-dependent vasodilation through transient receptor potential channels.

Ca2+ signaling of endothelial cells plays a critical role in controlling blood flow and pressure in small arteries and arterioles. As the impairment of endothelial function is closely associated with cardiovascular diseases (e.g., atherosclerosis, stroke, and hypertension), endothelial Ca2+ signaling mechanisms have received substantial attention. Increases in endothelial intracellular Ca2+ concentrations promote the synthesis and release of endothelial-derived hyperpolarizing factors (EDHFs, e.g., nitric oxide, prostacyclin, or K+ efflux) or directly result in endothelial-dependent hyperpolarization (EDH). These physiological alterations modulate vascular contractility and cause marked vasodilation in resistance arteries. Transient receptor potential (TRP) channels are nonselective cation channels that are present in the endothelium, vascular smooth muscle cells, or perivascular/sensory nerves. TRP channels are activated by diverse stimuli and are considered key biological apparatuses for the Ca2+ influx-dependent regulation of vasomotor reactivity in resistance arteries. Ca2+-permeable TRP channels, which are primarily found at spatially restricted microdomains in endothelial cells (e.g., myoendothelial projections), have a large unitary or binary conductance and contribute to EDHFs or EDH-induced vasodilation in concert with the activation of intermediate/small conductance Ca2+-sensitive K+ channels. It is likely that endothelial TRP channel dysfunction is related to the dysregulation of endothelial Ca2+ signaling and in turn gives rise to vascular-related diseases such as hypertension. Thus, investigations on the role of Ca2+ dynamics via TRP channels in endothelial cells are required to further comprehend how vascular tone or perfusion pressure are regulated in normal and pathophysiological conditions.

Physiological cyclic stretch up-regulates angiotensin-converting enzyme 2 expression to reduce proliferation and migration of vascular smooth muscle cells.

Angiotensin-converting enzyme 2 (ACE2) is considered as an endogenous negative regulator of renin–angiotensin system (RAS), exerting multiple cardiovascular protective roles. Whether mechanical stretch modulates ACE2 expression remains unknown. The present study aimed at investigating whether ACE2 is involved in physiological stretch (10% elongation, 1 Hz) mediated cellular functions and the underlying mechanism. Cultured human aortic smooth muscle cells (HASMCs) were exposed to 10% stretch for indicated time, and real-time PCR and Western blot analysis showed 10% stretch increased ACE2 expression and activity significantly compared with static conditions and increased Ang-(1-7) level, but decreased Ang II level; Brdu incorporation assay and Scratch test showed that ACE2 was involved in the inhibition of HASMCs proliferation and migration by 10% stretch; the Dual-Luciferase Reporter Assay demonstrated that 10% increased ACE2 promoter activity, but had no effect on ACE2 mRNA stability; kinase inhibition study and Electrophoretic mobility shift assay (EMSA) showed that JNK1/2 and PKCβII pathway, as well as their downstream transcription factors, AP-1 and NF-κB, were involved in 10% stretch induced ACE2 expression. In conclusion, our study indicates ACE2 is a mechanosensitive gene, and may represent a potential therapeutic target for mechanical forces related vascular diseases.

Angiopoietin-2 and vascular complications of type 2 diabetes

Cardiovascular diseases are the leading cause of death among patients with diabetes mellitus type 2 (T2DM), and microvascular complications of diabetes are associated with high morbidity and diminished quality of life. Angiopoietin-2 (Ang-2) is essential for endothelial physiology and plays an important role in vascular-related diseases. Its concentration in blood is elevated in patients with T2DM in comparison to those with normal glucose tolerance and in subjects with diabetic macrovascular complications compared to those without them. As for microvascular complications, it was found that serum Ang-2 concentration was significantly higher among T2DM patients with diabetic retinopathy compared to diabetic patients free of this complication. Moreover, in an animal model, Ang-2 mRNA expression was elevated in endothelial cells isolated from diabetic mice’s kidneys when compared to non-diabetic controls, which suggests its role in the development and progression of diabetic nephropathy. Targeting molecular Ang-2 pathway may become a therapeutic aim, especially that anti-angiogenic therapies are considered to be effective treatment methods in this field.

Effect of Hot Water Extracts of Maqui Berry on Human Aortic Endothelial Cells Exposed to a Hyperglycemic Environment

Abstract Objectives Impaired endothelial function is associated with many chronic vascular-related diseases including cardiovascular disease, inflammation, and diabetes. The antioxidant-rich Maqui berry (Aristotelia chilensis) has received increasing attention due to a variety of bioactivities including reduction of inflammation, control of blood glucose, and improvement of heart health, e.g., aortic endothelium, but corroborative research is needed. In the present study, we investigated the effects of aqueous Maqui berry extract (MBE) on nitric oxide (NO) production and oxidative stress (ROS) generation in human aortic endothelial cells (HAEC) alone or in a hyperglycemic environment with or without insulin. Methods Sterile (0.22 um filtered) MBE was added to endothelial basal medium (5% v/v) alone or containing glucose (final concentration 600 mg/dL; 33.3 mM) and/or insulin (final concentration 100 nM) followed by addition to monolayers and incubation for 24 hours. Monolayers were then assayed for NO production via the Greiss reaction, ROS via the use of DCFH-DA, and viability using MTT. Results We show that MBE may have increased ROS levels by 1.8-fold (P < 0.05) compared to control cultures using the DCFH-DA assay but decreased by ∼13% in the presence of glucose with or without insulin. MBE also increased NO levels by 3-fold (P < 0.05) compared to levels in control cultures. Glucose inclusion reduced NO by 15% and insulin reduced levels to that of control with or without glucose present. Viability, determined by MTT reduction, was not different between any of the groups. Conclusions The results suggest that water-soluble components of MB may modulate NO production in a hyperglycemic and/or hyperinsulinemic microenvironment and potentially improve endothelial function, in part, via the potential vasorelaxation properties of NO. Funding Sources School of Health Studies, University of Memphis.

Cross-Sectional Relationship between Carotid-Femoral Pulse Wave Velocity and Biomarkers in Vascular-Related Diseases.

Objectives The present study was done to investigate the relationship between carotid-femoral pulse wave velocity (CFPWV) and biomarkers such as homocysteine (Hcy), N-terminal pro-brain natriuretic peptide (NT-proBNP), and urine albumin (microalbumin) (UAE) in vascular-related diseases. Methods 656 subjects were enrolled into our study. There were 377 patients with hypertension, 231 with coronary heart disease, 154 with diabetes mellitus, and 186 healthy subjects. They were divided into four groups according to the number of suffered diseases: group 1 had only one of three diseases, group 2 had two, and group 3 had all of three diseases. CFPWV was measured by Complior apparatus. Results CFPWV was significantly higher in group 3 than in the healthy group, group 1, and group 2 (12.71 ± 2.38 vs 10.11 ± 2.28, 10.70 ± 2.12, and 11.92 ± 2.55, all p < 0.05). The level of Hcy was significantly higher in group1, group 2, and group 3 than in healthy subjects, respectively. Levels of Log NT-proBNP and Log UAE were significantly higher in group 3 than in group 1 (2.27 ± 0.4 vs 2.10 ± 0.4, 1.00 ± 0.65 vs 0.68 ± 0.56, both p < 0.05). Positive correlation between CFWV and Hcy, Log UAE, and Log NT-proBNP was found in the entire study group (r = 0.109, 0.196, and 0.119, all p < 0.05). Multivariate analysis showed that pulse pressure, age, fasting plasma glucose, diastolic blood pressure, body mass index, and Log UAE were independent associating factors of CFPWV in all subjects (β = 0.334, p < 0.001; β = 0.333, p < 0.001; β = 0.126, p=0.004; β = 0.137, p=0.003; β = −0.142, p=0.002; and β = 0.098, p=0.031). Conclusions CFPWV was significantly higher in subjects with hypertension, CHD, and DM. There was correlation between CFPWV and biomarkers such as NT-proBNP, Hcy, and urine albumin (microalbumin).

Expression of Nik-related kinase in smooth muscle cells attenuates vascular inflammation and intimal hyperplasia.

Inflammation of the vascular microenvironment modulates distinct types of vascular cells, and plays important roles in promoting atherosclerosis, stenosis/restenosis, and vascular-related diseases. Nik-related kinase (Nrk), a member of the Ste20-type kinase family, has been reported to be selectively expressed in embryonic skeletal muscle. However, whether Nrk is expressed in adult vascular smooth muscle, and if it influences intimal hyperplasia is unclear. Here, we found that Nrk is abundantly expressed in cultured vascular smooth muscle cells (VSMC) and mouse arterial intima. Treatment of mouse VSMCs with lipopolysaccharide (LPS) or platelet-derived growth factor significantly reduced Nrk expression. In addition, expression of Nrk was significantly reduced in regions of neointimal formation caused by guide-wire carotid artery injuries in mice, as well as in human atherosclerotic tissues, when compared to normal vessels. We identified that expression of matrix metalloproteinases (MMP3, MMP8 and MMP12) and inflammatory cytokines/chemokines (CCL6, CCL8, CCL11, CXCL1, CXCL3, CXCL5 and CXCL9) are synergistically induced by Nrk siRNA in LPS-treated mouse VSMCs. Moreover, we found that resveratrol significantly impaired LPS- and Nrk siRNA-induced expression of MMP3, CCL8, CCL11, CXCL3 and CXCL5. These results suggested that Nrk may play important roles in regulating pathological progression of atherosclerosis or neointimal- hyperplasia-related vascular diseases.

Protective Effect of Diosgenin on Streptozotocin Induced Diabetic Nephropathy in Experimental Rats

Diabetes mellitus is a multifactorial metabolic disorder associated with the diabetes related vascular diseases. Oxidative stress along with inflammation is the Key factor leading to diabetic complications. Present study was designed to investigate the protective role of diosgenin, a steroidal saponin, in diabetes induced early kidney injury and oxidative stress markers and histopathological changes in kidney of diabetic rats, induced by single intra-peritoneal injection of streptozotocin (55 mg/kg weight (b.w.). After 72 hrs, experimental rats received diosgenin at different doses (10, 20 and 40 mg/kg b.w.) once daily for four weeks. At the end of the experiment, diabetic rats showed a significant increase in the levels of plasma glucose, glycosylated hemoglobin with a significant decrease in insulin and total hemoglobin. The activities of antioxidant enzymes such as superoxide dismutase, catalase, reduced glutathione, and the levels of reduced glutathione were decreased while increases in the levels of lipid peroxidation markers were observed in kidney tissues of diabetic rats. Oral administration of diosgenin to diabetic rats considerably shrivelled the plasma glucose and exaggerated the endocrine level supported a dose dependent manner. Diosgenin at a dose of 40 mg/kg b.w. was more pronounced effect than the other two doses and used for further studies. All the manifestations observed in diabetic rats were significantly reversed to near normal at a dose of 40 mg/kg b.w. of diosgenin. These findings recommend that diosgenin may have a helpful role against excretory organ harm evoked by aerobic stress within the diabetic state.

Automatic protocol for quantifying the vasoconstriction in blood vessel images.

Vascular targeted photodynamic therapy (V-PDT) has been successfully utilized for various vascular-related diseases. To optimize the PDT dose and treatment protocols for clinical treatments and to elucidate the biological mechanisms for V-PDT, blood vessels in the dorsal skin-fold window chamber (DSWC) of nude mice are often chosen to perform in vivo studies. In this study, a new automatic protocol to quantify the vasoconstriction of blood vessels in the DSWC model is proposed, which focused on tracking the pixels of blood vessels in pre- V-PDT images that disappear after V-PDT. The disappearing pixels indicate that the blood vessels were constricted, and thus, the vasoconstriction image for pixel distribution can be constructed. For this, the image of the circular region of interest was automatically extracted using the Hough transform. In addition, the U-Net model is employed to segment the image, and the Speeded-Up Robust Features algorithm to automatically register the segmented pre- and post- V-PDT images. The vasoconstriction of blood vessels in the DSWC model after V-PDT is directly quantified, which can avoid by the potential of generating new capillaries. The accuracy, sensitivity and specificity of the U-Net model for image segmentation are 90.64%, 80.12% and 92.83%, respectively. A significant difference in vasoconstriction between a control and a V-PDT group was observed. This new automatic protocol is well suitable for quantifying vasoconstriction in blood vessel image, which holds the potential application in V-PDT studies.

Nepeta angustifolia C. Y. Wu improves renal injury in HFD/STZ-induced diabetic nephropathy and inhibits oxidative stress-induced apoptosis of mesangial cells

Ethnopharmacological relevanceAs an important medicinal material constituting a variety of traditional Chinese medicine prescriptions, Nepeta angustifolia C. Y. Wu was used as a folk medicine to treat various vascular-related diseases including apoplexia, and cerebral haemorrhage in Tibet, China. Our previous studies have shown that this plant had a significant protective effect on vascular dysfunction of the intracerebral haemorrhage and diabetic rats. In present study, we aimed to investigate the protective effects and underlying mechanisms of Nepeta angustifolia on diabetic nephropathy (DN), a microvascular complication. Aim of the studyThis study is aim to evaluate the protective effect of ethanol extracts of N. angustifolia (NA) on DN, and explore mechanism of action to provide basis for its pharmacological action against DN. Materials and methodsHigh-fat diet and low-dose streptozotocin administration (HFD/STZ) induced diabetic rats were randomly divided into 5 groups (n = 8): the diabetic model group, metformin group, and three dose groups of NA (60 mg/kg, 120 mg/kg, 240 mg/kg). After administration of NA for 8 weeks, the blood, urine and renal tissue were collected for subsequent experiments. Biochemical markers (urine protein, Cr, BUN), oxidative stress makers (SOD, GSH-px and MDA) and pro-inflammatory mediators (TNF-α, IL-1β, IL-6 and MCP-1) were evaluated by commercial kit and ELISA, respectively. The effect of NA on DN was further confirmed by evaluation of renal histopathology by using the H&E, PAS and Masson staining. The H2O2-induced HBZY-1 cells (rat glomerular mesangial cells) were also been used to evaluate the renal protective effect of NA (50 μg/mL, 100 μg/mL, 200 μg/mL). The oxidative stress makers were detected by commercial kit. The levels of apoptosis and related proteins (caspase 3, 9) were detected by TUNEL assay and western blot analysis, respectively. The depolarization of mitochondrial membrane potential was detected by JC-1 staining assay. ResultsThe administration of NA is helpful to maintain near normal body weight, blood glucose, urine volume, urine protein, kidney index and serum levels of Cr and BUN. NA treatment significantly improve renal dysfunction by the down-regulation of renal oxidative stress and pro-inflammatory mediators in HFD/STZ induced diabetic rats. In vitro experiments, NA has a significant cellular protective effect in H2O2-induced HBZY-1 cells, as well as the regulation in increases of SOD level and the decreases of ROS and MDA levels. Furthermore, NA treatment can significantly inhibit H2O2 induced mesangial cells apoptosis by the increasing mitochondrial potential and suppressing caspases-madiated signaling pathway. ConclusionsNA has obvious improvement on renal dysfunction in HFD/STZ induced diabetic rats. NA can protect mesangial cells by inhibiting oxidative stress induced apoptosis, which may be related to its regulation of mitochondrial-caspase apoptosis pathway.

Injectable biodegradable bi-layered capsule for sustained delivery of bevacizumab in treating wet age-related macular degeneration

Vascular endothelial growth factor (VEGF) is a key regulator of abnormal blood vessel growth. As such, bevacizumab-based inhibition of VEGF has been the clinically adopted strategy to treat colorectal and breast cancers as well as age-related macular degeneration (AMD). However, as the treatment of vascular diseases often requires a high drug concentration for a long period, the burst release of bevacizumab remains a critical limitation in anti-VEGF-based therapies. Maintaining bevacizumab at high concentrations over extended periods remains challenging due to insufficient drug loading capacity and drug-device interactions. We report the development of a polymeric based bi-layered capsule that could address these challenges by extending the release over one year, thereby providing an effective platform enabling treatment of chronic vascular diseases. Remarkably, the developed capsules have a bi-layered structure which ensures the structural integrity of the injectable capsules and appropriate diffusion of bevacizumab by providing optimal physical trapping and electrostatic interaction. Meanwhile, the central hollow design enables a higher drug loading to meet the need for long-term release of bevacizumab for several months to one year. Using an in vitro drug release assay, we demonstrated that the bi-layered capsule could produce longer-term local drug administration by intravitreal injection compared to previously reported devices. The capsules also present minimal toxicity and maintain anti-VEGF potency, suggesting that our approach may have the potential to treat vascular-related diseases using bevacizumab.

Roles and Functions of Exosomal Non-coding RNAs in Vascular Aging.

Aging is a progressive loss of physiological integrity and functionality process which increases susceptibility and mortality to diseases. Vascular aging is a specific type of organic aging. The structure and function changes of endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are the main cause of vascular aging, which could influence the threshold, process, and severity of vascular related diseases. Accumulating evidences demonstrate that exosomes serve as novel intercellular information communicator between cell to cell by delivering variety biologically active cargos, especially exosomal non-coding RNAs (ncRNAs), which are associated with most of aging-related biological and functional disorders. In this review, we will summerize the emerging roles and mechanisms of exosomal ncRNAs in vascular aging and vascular aging related diseases, focusing on the role of exosomal miRNAs and lncRNAs in regulating the functions of ECs and VSMCs. Moreover, the relationship between the ECs and VSMCs linked by exosomes, the potential diagnostic and therapeutic application of exosomes in vascular aging and the clinical evaluation and treatment of vascular aging and vascular aging related diseases will also be discussed.

RELMα Licenses Macrophages for Damage-Associated Molecular Pattern Activation to Instigate Pulmonary Vascular Remodeling.

Pulmonary hypertension (PH) is a debilitating disease characterized by remodeling of the lung vasculature. In rodents, resistin-like molecule-α (RELMα, also known as HIMF or FIZZ1) can induce PH, but the signaling mechanisms are still unclear. In this study, we used human lung samples and a hypoxia-induced mouse model of PH. We found that the human homolog of RELMα, human (h) resistin, is upregulated in macrophage-like inflammatory cells from lung tissues of patients with idiopathic PH. Additionally, at PH onset in the mouse model, we observed RELMα-dependent lung accumulation of macrophages that expressed high levels of the key damage-associated molecular pattern (DAMP) molecule high-mobility group box 1 (HMGB1) and its receptor for advanced glycation end products (RAGE). In vitro, RELMα/hresistin-induced macrophage-specific HMGB1/RAGE expression and facilitated HMGB1 nucleus-to-cytoplasm translocation and extracellular secretion. Mechanistically, hresistin promoted HMGB1 posttranslational lysine acetylation by preserving the NAD+-dependent deacetylase sirtuin (Sirt) 1 in human macrophages. Notably, the hresistin-stimulated macrophages promoted apoptosis-resistant proliferation of human pulmonary artery smooth muscle cells in an HMGB1/RAGE-dependent manner. In the mouse model, RELMα also suppressed the Sirt1 signal in pulmonary macrophages in the early posthypoxic period. Notably, recruited macrophages in the lungs of these mice carried the RELMα binding partner Bruton tyrosine kinase (BTK). hResistin also mediated the migration of human macrophages by activating BTK in vitro. Collectively, these data reveal a vascular-immune cellular interaction in the early PH stage and suggest that targeting RELMα/DAMP-driven macrophages may offer a promising strategy to treat PH and other related vascular inflammatory diseases.

Specific Signatures of Serum miRNAs as Potential Biomarkers to Discriminate Clinically Similar Neurodegenerative and Vascular-Related Diseases.

Neurodegenerative diseases (NDs) are age-dependent; among them, Alzheimer's disease (AD) and Parkinson's disease (PD) are the most frequent. Similarly, cerebrovascular damage can induce the development of vascular-related disorders that share common features with AD and PD, respectively, named vascular dementia (VD) and vascular parkinsonism (VP). To date, ND diagnosis is mainly clinical; therefore, since these disorders show similar symptoms, their correct discrimination may be difficult. We detected 23 ND-associated microRNAs (miRNAs) by literature mining and investigated their serum expression in a cohort of 139 patients including AD, PD, VD, and VP patients and healthy controls. TaqMan RT-PCR data showed that miR-23a upregulation was associated with an ongoing neurodegenerative process, similar to miR-22* and miR-29a, while let-7d, miR-15b, miR-24, miR-142-3p, miR-181c, and miR-222 showed an altered expression in Parkinson-like phenotypes, as well as miR-34b, miR-125b, and miR-130b in Alzheimer-like disorders. By computing logistic regression models and ROC curves, we identified signatures of neuro-miRNAs specific for each disease, showing good diagnostic performance. Interestingly, we found that miR-23a, miR-29a, miR-34b, and miR-125b exhibited a different distribution between exosomes and vesicle-free serum, suggesting a heterogeneity of secretion for these miRNAs. Our results suggest that miRNA signatures could discriminate in a non-invasive manner neurodegenerative disorders, thus improving clinical diagnoses.

Pediatric Pulmonary Hypertension on the World Stage: Do We Need Separate Neonatal Guidelines?

Pediatric Pulmonary Hypertension on the World Stage: Do We Need Separate Neonatal Guidelines?

A genome-wide association study implicates multiple mechanisms influencing raised urinary albumin-creatinine ratio.

Raised albumin–creatinine ratio (ACR) is an indicator of microvascular damage and renal disease. We aimed to identify genetic variants associated with raised ACR and study the implications of carrying multiple ACR-raising alleles with metabolic and vascular-related disease. We performed a genome-wide association study of ACR using 437 027 individuals from the UK Biobank in the discovery phase, 54 527 more than previous studies, and followed up our findings in independent studies. We identified 62 independent associations with ACR across 56 loci (P < 5 × 10–8), of which 20 were not previously reported. Pathway analyses and the identification of 20 of the 62 variants (at r2 > 0.8) coinciding with signals for at least 16 related metabolic and vascular traits, suggested multiple pathways leading to raised ACR levels. After excluding variants at the CUBN locus, known to alter ACR via effects on renal absorption, an ACR genetic risk score was associated with a higher risk of hypertension, and less strongly, type 2 diabetes and stroke. For some rare genotype combinations at the CUBN locus, most individuals had ACR levels above the microalbuminuria clinical threshold. Contrary to our hypothesis, individuals carrying more CUBN ACR-raising alleles, and above the clinical threshold, had a higher frequency of vascular disease. The CUBN allele effects on ACR were twice as strong in people with diabetes—a result robust to an optimization-algorithm approach to simulating interactions, validating previously reported gene–diabetes interactions (P ≤ 4 × 10–5). In conclusion, a variety of genetic mechanisms and traits contribute to variation in ACR.

Is serum total bilirubin a predictor of prognosis in arteriosclerotic cardiovascular disease? A meta-analysis.

The protective role of serum total bilirubin, a widely recognized antioxidant, has been approved by numerous updating studies. However, regarding the effect of high serum total bilirubin level (STBL) in arteriosclerotic cardiovascular disease (ASCVD) are conflicting in different sources of data. We, therefore, performed this meta-analysis to evaluate the influence of STBL on risk of ASCVD.Four databases were used to identify the literature with a date of search of January, 2019. Finally, a total of 20 studies had been adopted. ASCVD was defined as acute coronary syndrome, stable angina, coronary revascularization, atherosclerotic stroke or transient ischemic attack, and peripheral arterial disease (PAD). All relevant data were collected from studies meeting the inclusion criteria.A total of 20 published studies (323,891 cases) met the inclusion criteria. The meta-analysis revealed that, in studies excluding heterogeneity, STBL was significantly positively related to in-hospital cardiovascular mortality (odds ratio [OR] 2.82, 95% confidence interval [CI] 1.83–4.36, Z = 4.69, P < .001) and major adverse cardiac events (OR 1.88, 95% CI 1.414–2.491, Z = 4.36, P < .001), also negatively associated with prognosis of acute myocardial infarction, pooled hazard ratio (HR) = 0.804 (95% CI 0.700–0.923, Z = 3.08, P = .002). The correlation similarity was also reflected in terms of patients with stroke (HR 0.78, 95% CI 0.70–0.88, Z = 4.24, P = .003). Combined analysis revealed that lower STBL was significantly associated with PAD, pooled OR = 0.91 (95% CI 0.85–0.98, Z = 2.39, P = .017). In general analysis, a conclusion can be drawn, that higher STBL was significantly negative correlated with cardiovascular disease, pooled HR = 0.83 (95% CI 0.73–0.94, Z = 3.02, P = .003).Higher STBL significantly improved the prognosis of ASCVD; furthermore, STBL was an important factor in the long-term prognosis of vascular-related disease prevention and can be used as a predictor in vascular-related disease risk prediction.

NIR-II-Excited Intravital Two-Photon Microscopy Distinguishes Deep Cerebral and Tumor Vasculatures with an Ultrabright NIR-I AIE Luminogen.

Intravital fluorescence imaging of vasculature morphology and dynamics in the brain and in tumors with large penetration depth and high signal-to-background ratio (SBR) is highly desirable for the study and theranostics of vascular-related diseases and cancers. Herein, a highly bright fluorophore (BTPETQ) with long-wavelength absorption and aggregation-induced near-infrared (NIR) emission (maximum at ≈700 nm) is designed for intravital two-photon fluorescence (2PF) imaging of a mouse brain and tumor vasculatures under NIR-II light (1200 nm) excitation. BTPETQ dots fabricated via nanoprecipitation show uniform size of around 42 nm and a high quantum yield of 19 ± 1% in aqueous media. The 2PF imaging of the mouse brain vasculatures labeled by BTPETQ dots reveals a 3D blood vessel network with an ultradeep depth of 924 µm. In addition, BTPETQ dots show enhanced 2PF in tumor vasculatures due to their unique leaky structures, which facilitates the differentiation of normal blood vessels from tumor vessels with high SBR in deep tumor tissues. Moreover, the extravasation and accumulation of BTPETQ dots in deep tumor (more than 900 µm) is visualized under NIR-II excitation. This study highlights the importance of developing NIR-II light excitable efficient NIR fluorophores for in vivo deep tissue and high contrast tumor imaging.

Cerebellar artery arising from the cavernous segment of the internal carotid artery and persistent trigeminal artery: a spectrum of incomplete longitudinal fusion.

Background The embryological relationship between cerebellar arteries originating directly from the cavernous segment of the internal carotid artery and persistent trigeminal artery is not well understood. Purpose To evaluate the incidence and pattern of cerebellar arteries originating from the internal carotid artery and persistent trigeminal artery, and to discuss their probable embryological relationship. Material and Methods We reviewed 5113 angiographic studies from 5093 patients at our institution over the last eight years, searching for patients with persistent trigeminal artery and cerebellar arteries originating from a cavernous segment of internal carotid artery (persistent trigeminal artery variant). Results Of the 5093 patients, 27 patients had persistent trigeminal artery or persistent trigeminal artery variant (0.53%). Twenty patients (6 men, 14 women; median age = 54 years) had persistent trigeminal artery (0.39%). Seven patients (2 men, 5 women, age range = 37–72 years; median age = 57 years) had a persistent trigeminal artery variant with persistent trigeminal artery terminating in a cerebellar artery without direct connection to the basilar artery (persistent trigeminal artery variant; 0.14%). The terminal branch of the persistent trigeminal artery variant was an anterior inferior carotid artery in five patients and a superior cerebellar artery in two patients. Of the seven patients having persistent trigeminal artery variant, four patients had another artery from the basilar artery to the anterior inferior carotid artery territory. In 6/20 patients with persistent trigeminal artery, there was an anterior inferior carotid artery arising from the persistent trigeminal artery. One of these patients showed another arterial branch from the basilar artery to the anterior inferior carotid artery territory. Conclusion Persistent trigeminal artery variant and cerebellar arteries originating from the persistent trigeminal artery are both believed to be a spectrum of incomplete fusion of the longitudinal neural arteries. Understanding the precise anatomy is important in diagnostic and therapeutic settings for related vascular disease.

Are Platelet Indices such as Platelet Volume, Platelet Distribution Width, and Plateletcrit Associated with Peyronie Disease?

PurposePeyronie disease (PD) occurs as a result of recurrent microvascular injuries or trauma of the tunica albuginea, although its precise etiology is unknown. Mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT), which are parameters indicative of platelet activity, are considered to be functional markers of platelets involved in the pathophysiology of related inflammatory and vascular diseases. In this study, we aimed to examine the relationship between PD and platelet indices.Materials and MethodsWe evaluated participants who presented to the andrology department of our institution between December 2015 and May 2018. Ninety-two men with PD and 80 healthy volunteers were included in this study. Participants who had received medical treatment affecting platelets or had any hematologic or systemic diseases were excluded from the study.ResultsThe mean age of men with PD was 53.8±10.2 years, and the mean age of the control group was 52.2±8.0 years (p=0.465). There were no significant differences in the mean IIEF-5 scores, platelet count, MPV, PDW, or PCT between the patients with and without PD (p<0.05).ConclusionsNo correlations were found between PD and platelet indices. Large-scale prospective cross-sectional studies are needed to elucidate the etiopathogenesis of PD.