Martin Hultman , Freya Richter , Marcus Larsson , Tomas Strömberg , Fredrik Iredahl , Ingemar Fredriksson
{"title":"Robust analysis of microcirculatory flowmotion during post-occlusive reactive hyperemia","authors":"Martin Hultman , Freya Richter , Marcus Larsson , Tomas Strömberg , Fredrik Iredahl , Ingemar Fredriksson","doi":"10.1016/j.mvr.2024.104715","DOIUrl":"10.1016/j.mvr.2024.104715","url":null,"abstract":"<div><h3>Background</h3><p>Flowmotion analysis of the microcirculatory blood flow is a method to extract information about the vessel regulatory function. It has previously shown promise when applied to measurements during a post-occlusive reactive hyperemia. However, the reperfusion peak and the following monotonic decline introduces false low frequencies that should not be interpreted as rhythmic vasomotion effect.</p></div><div><h3>Aim</h3><p>To develop and validate a robust method for flowmotion analysis of post-occlusive reactive hyperemia signals.</p></div><div><h3>Method</h3><p>The occlusion-induced reperfusion response contains a typical rapid increase followed by a monotonic decline to baseline. A mathematical model is proposed to detrend this transient part of the signal to enable further flowmotion analysis. The model is validated in 96 measurements on healthy volunteers.</p></div><div><h3>Results</h3><p>Applying the proposed model corrects the flowmotion signal without adding any substantial new false flowmotion components.</p></div><div><h3>Conclusion</h3><p>Future studies should use the proposed method or equivalent when analyzing flowmotion during post-occlusive reactive hyperemia to ensure valid results.</p></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"155 ","pages":"Article 104715"},"PeriodicalIF":2.9,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0026286224000645/pdfft?md5=7d651a301c23ab5f41ab56bccc58e142&pid=1-s2.0-S0026286224000645-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xuenan Zhuang , Jiaxin Pu , Miaoling Li , Lan Mi , Xiongze Zhang , Yuying Ji , Yining Zhang , Guiqin He , Xuelin Chen , Yunkao Zeng , Yongyue Su , Yuhong Gan , Xinlei Hao , Feng Wen
{"title":"Association between three-dimensional morphological features and functional indicators of neovascular age-related macular degeneration","authors":"Xuenan Zhuang , Jiaxin Pu , Miaoling Li , Lan Mi , Xiongze Zhang , Yuying Ji , Yining Zhang , Guiqin He , Xuelin Chen , Yunkao Zeng , Yongyue Su , Yuhong Gan , Xinlei Hao , Feng Wen","doi":"10.1016/j.mvr.2024.104716","DOIUrl":"10.1016/j.mvr.2024.104716","url":null,"abstract":"<div><h3>Purpose</h3><p>To investigate the correlation between morphological lesions and functional indicators in eyes with neovascular age-related macular degeneration (nAMD).</p></div><div><h3>Methods</h3><p>This was a prospective observational study of treatment-naïve nAMD eyes. Various morphological lesions and impaired retinal structures were manually measured at baseline and month-3 in three-dimensional optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) images, including the volumes (mm<sup>3</sup>) of macular neovascularization (MNV), avascular subretinal hyperreflective material (avascular SHRM), subretinal fluid (SRF), intraretinal fluid (IRF), serous pigment epithelial detachment (sPED) and the impaired area (mm<sup>2</sup>) of ellipsoid zone (EZ), external limiting membrane (ELM) and outer nuclear layer (ONL).</p></div><div><h3>Results</h3><p>Sixty-three eyes were included. The volume of avascular SHRM showed persistent positive associations with the area of EZ damage, both at baseline, month-3, and change values (all <em>P</em> < 0.001). Poor BCVA (month-3) was associated with larger volumes of baseline IRF (β = 0.377, <em>P</em> < 0.001), avascular SHRM (β = 0.306, <em>P</em> = 0.032), and ELM impairment area (β = 0.301, <em>P</em> = 0.036) in multivariate model. EZ and ELM impairment were primarily associated with baseline avascular SHRM (β = 0.374, <em>p</em> = 0.003; β = 0.388, <em>P</em> < 0.001, respectively), while ONL impairment primarily associated with MNV (β = 0.475, <em>P</em> < 0.001).</p></div><div><h3>Conclusion</h3><p>The utilization of three-dimensional measurements elucidates the intrinsic connections among various lesions and functional outcomes. In particular, avascular SHRM plays an important role in prognosis of nAMD.</p></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"155 ","pages":"Article 104716"},"PeriodicalIF":2.9,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Thymic stromal lymphopoietin and digital microvascular damage in systemic sclerosis patients: A pilot study","authors":"Chiara Pellicano , Giuseppina Cusano , Umberto Basile , Edoardo Rosato","doi":"10.1016/j.mvr.2024.104714","DOIUrl":"10.1016/j.mvr.2024.104714","url":null,"abstract":"<div><h3>Background</h3><p>Systemic sclerosis (SSc) is a complex autoimmune connective-tissue disease, characterised by vasculopathy and fibrosis of the skin and internal organs. Activation of microvascular endothelial cells (ECs) causes the intimal hyperplasia that characterises the vascular remodelling in SSc. The most frequent complication of SSc is the development of digital ulcers (DUs). Thymic stromal lymphopoietin (TSLP) may trigger fibrosis and sustain vascular damage. Aim of this study was to evaluate the correlation between serum level of TSLP and DUs.</p></div><div><h3>Methods</h3><p>75 consecutive SSc patients were enrolled and serum TSLP levels were measured. The presence of history of DUs (HDU) was evaluated. Recurrent new DUs were defined as the presence of at least 3 episodes of DUs in a 12-months follow up period. The risk of developing new DUs was calculated by applying the capillaroscopic skin ulcer risk index (CSURI).</p></div><div><h3>Results</h3><p>The median value of TSLP was higher in patients with HDU than patients without HDU [181.67 pg/ml (IQR 144.67; 265.66) vs 154.67 pg/ml (IQR 110.67; 171.33), <em>p</em> < 0.01]. The median value of TSLP was higher in patients with an increased CSURI index than patients without an increased CSURI [188 pg/ml (IQR 171.33; 246.33) vs 159.33 pg/ml (IQR 128.67; 218), <em>p</em> < 0.01]. Kaplan-Meier curves demonstrated that free survival from new DUs was significantly (p < 0.01) lower in SSc patients with increased TSLP serum levels.</p></div><div><h3>Conclusion</h3><p>TSLP might have a key role in digital microvascular damage of SSc patients.</p></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"155 ","pages":"Article 104714"},"PeriodicalIF":2.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0026286224000633/pdfft?md5=26f610abc3935221245fe1a9ba5948ee&pid=1-s2.0-S0026286224000633-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bulent Ergin , Aysegul Kapucu , Lakhmir Chawla , Can Ince
{"title":"Synthetic Angiotensin II ameliorates alterations of systemic hemodynamics, microcirculatory deterioration, and renal damage in septic rats","authors":"Bulent Ergin , Aysegul Kapucu , Lakhmir Chawla , Can Ince","doi":"10.1016/j.mvr.2024.104709","DOIUrl":"10.1016/j.mvr.2024.104709","url":null,"abstract":"<div><h3>Introduction</h3><p>Septic shock is a systemic infection that causes persistent systemic hypotension, inflammation, tissue hypoperfusion and acute kidney injury (AKI). Despite norepinephrine being the currently recommended vasopressor agent, an alternative vasopressor agent that positively affects peripheral and organ microcirculatory perfusion and oxygenation is needed. This study investigated a new synthetic Angiotensin II agent suitable for improving microcirculatory parameters in a rat model of sepsis-induced systemic hemodynamic dysfunction.</p></div><div><h3>Methods</h3><p>48 mechanically ventilated, anesthetized male rats were allocated as control; lipopolysaccharide (LPS, 20 mg/kg) and LPS groups received either ringer acetate (RA), norepinephrine (NE), Angiotensin II (Ang II), or a combination of NE and Ang II. Systemic hemodynamics, renal cortical pO<sub>2</sub> and perfusion, and muscle microcirculatory oxygen saturation were evaluated.</p></div><div><h3>Results</h3><p>MAP was restored in all LPS groups that received Ang II, NE, and NE + Ang II compared to the LPS group alone (<em>p</em> < 0.05). The deterioration of renal microcirculatory cortical oxygen, oxygen delivery, and consumption after sepsis was not restored by any of the resuscitation strategies. However, urine output was improved after Ang II resuscitation compared to the LPS and LPS + RA groups (<em>p</em> < 0.05). Furthermore, the muscle capillary oxygen saturation and functional capillary density (FCD) were improved by a combined infusion of NE and Ang II (<em>p</em> < 0.05).</p></div><div><h3>Conclusions</h3><p>Ang II can improve the MAP in rats in a way comparable to norepinephrine. Ang II increased urine output and muscle capillary oxygenation and reduced renal tissue damage. Our study supports that broad-spectrum vasopressors can benefit tissue perfusion and oxygenation in the resuscitation of septic patients.</p></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"155 ","pages":"Article 104709"},"PeriodicalIF":2.9,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S002628622400058X/pdfft?md5=75a13c54e388e554f9cf06e7e88c410c&pid=1-s2.0-S002628622400058X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Oxidative stress and vascular dysfunction: Potential therapeutic targets and therapies in peripheral artery disease","authors":"Michael F. Allen , Song-Young Park , Yi-sub Kwak","doi":"10.1016/j.mvr.2024.104713","DOIUrl":"10.1016/j.mvr.2024.104713","url":null,"abstract":"<div><p>Peripheral artery disease (PAD) is the manifestation of atherosclerosis characterized by the accumulation of plaques in the arteries of the lower limbs. Interestingly, growing evidence suggests that the pathology of PAD is multifaceted and encompasses both vascular and skeletal muscle dysfunctions, which contributes to blunted physical capabilities and diminished quality of life. Importantly, it has been suggested that many of these pathological impairments may stem from blunted reduction-oxidation (redox) handling. Of note, in those with PAD, excessive production of reactive oxygen species (ROS) outweighs antioxidant capabilities resulting in oxidative damage, which may have systemic consequences. It has been suggested that antioxidant supplementation may be able to assist in handling ROS. However, the activation of various ROS production sites makes it difficult to determine the efficacy of these antioxidant supplements. Therefore, this review focuses on the common cellular mechanisms that facilitate ROS production and discusses how excessive ROS may impair vascular and skeletal muscle function in PAD. Furthermore, we provide insight for current and potential antioxidant therapies, specifically highlighting activation of the Kelch-like ECH-associated protein 1 (Keap1) - Nuclear Factor Erythroid 2-related factor 2 (Nrf2) pathway as a potential pharmacological therapy to combat ROS accumulation and aid in vascular function, and physical performance in patients with PAD. Altogether, this review provides a better understanding of excessive ROS in the pathophysiology of PAD and enhances our perception of potential therapeutic targets that may improve vascular function, skeletal muscle function, walking capacity, and quality of life in patients with PAD.</p></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"155 ","pages":"Article 104713"},"PeriodicalIF":2.9,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nail fold capillaroscopy in leprosy: Unveiling the microvascular changes","authors":"Bharti Aggarwal , Vijay Gandhi , Archana Singal , Amitesh Aggarwal , Sushobhan Saha","doi":"10.1016/j.mvr.2024.104712","DOIUrl":"10.1016/j.mvr.2024.104712","url":null,"abstract":"<div><h3>Background</h3><p>Leprosy, a chronic infectious disease, is associated with various nail changes. Its etiopathogenesis is multifaceted, with microvascular damage being crucial. Nail fold capillaroscopy (NFC) emerges as a novel tool for detecting early vascular deficits in leprosy. The study aimed to assess and provide a complete clinical characterization of NFC changes in leprosy patients.</p></div><div><h3>Methods</h3><p>It is an observational cross-sectional study, done over a period of 1.5 year (January 2021 to august 2022) in a tertiary care hospital, encompassing 60 patients diagnosed with leprosy (18–60 years). After obtaining informed consent; detailed history, complete cutaneous and neurological examinations were conducted. All fingernails and toenails were examined for clinical changes. Subsequently, onychoscopy was performed using USB type of video-dermatoscope (Model AM7115MZT Dino-lite), a non-invasive tool. This was followed by NFC which was done for all fingernails and images were recorded by single operator, which were then assessed for quantitative and qualitive changes and statistical analysis was conducted using SPSS v20, with mean capillary density compared using Student's <em>t</em>-test, morphological change frequencies assessed by proportions, and group comparisons made using Chi-square or Fischer exact tests, with a significance threshold of <em>p</em> < 0.05.</p></div><div><h3>Results</h3><p>Among the 60 patients, 39 were in the lepromatous group, which included both borderline lepromatous (BL) and lepromatous leprosy (LL) patients, and 17 were in the tuberculoid group, which included borderline tuberculoid (BT) leprosy patients; 23.3 % had Type 1 reactions, and 18.3 % had Type 2 reactions. Nail fold capillaroscopy (NFC) showed microvasculature changes in 93.3 % of patients. The average capillary density was 6.8 ± 1.5 capillaries per mm, with the lepromatous group having a lower density (6.5 ± 1.09) compared to the tuberculoid group (7.0 ± 0.86). The most common NFC changes in the tuberculoid group were tortuous capillaries (70 %), capillary dropouts, and dilated capillaries (both 64.7 %). In the lepromatous group, capillary dropouts (82 %) were most frequent, followed by tortuous (69 %), receding (69 %), and dilated capillaries (66 %). A dilated and prominent subpapillary plexus was more common in the lepromatous group (35 %, <em>p</em> = 0.04). Patients with trophic changes in the lepromatous group had more capillary dropouts and bizarre capillaries. Capillary dropouts, dilated capillaries, and visible subpapillary venous plexus were more prevalent in patients with Type 2 reactions.</p></div><div><h3>Conclusion</h3><p>NFC changes are prevalent in both tuberculoid and lepromatous leprosy, which may be an indicator of peripheral vascular compromise and trophic changes, especially in lepromatous leprosy. NFC can be an auxiliary tool for detecting microvascular abnormalities in leprosy patients.</p></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"155 ","pages":"Article 104712"},"PeriodicalIF":2.9,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhen Yang , Yingrui Li , Mengying Huang , Xin Li , Xuehui Fan , Chen Yan , Zenghui Meng , Bin Liao , Nazha Hamdani , Ibrahim El-Battrawy , Xiaoli Yang , Xiaobo Zhou , Ibrahim Akin
{"title":"Small conductance calcium-activated potassium channel contributes to stress induced endothelial dysfunctions","authors":"Zhen Yang , Yingrui Li , Mengying Huang , Xin Li , Xuehui Fan , Chen Yan , Zenghui Meng , Bin Liao , Nazha Hamdani , Ibrahim El-Battrawy , Xiaoli Yang , Xiaobo Zhou , Ibrahim Akin","doi":"10.1016/j.mvr.2024.104699","DOIUrl":"10.1016/j.mvr.2024.104699","url":null,"abstract":"<div><p>Patients with Takotsubo syndrome displayed endothelial dysfunction, but underlying mechanisms have not been fully clarified. This study aimed to explore molecular signalling responsible for catecholamine excess induced endothelial dysfunction.</p><p>Human cardiac microvascular endothelial cells were challenged by epinephrine to mimic catecholamine excess. Patch clamp, FACS, ELISA, PCR, and immunostaining were employed for the study.</p><p>Epinephrine (Epi) enhanced small conductance calcium-activated potassium channel current (I<sub>SK1</sub><sub>–</sub><sub>3</sub>) through activating α1 adrenoceptor. Phenylephrine enhanced edothelin-1 (ET-1) and reactive oxygen species (ROS) production, and the effects involved contribution of I<sub>SK1</sub><sub>–</sub><sub>3</sub>. H<sub>2</sub>O<sub>2</sub> enhanced I<sub>SK1</sub><sub>–</sub><sub>3</sub> and ET-1 production. Enhancing I<sub>SK1</sub><sub>–</sub><sub>3</sub> caused a hyperpolarization, which increases ROS and ET-1 production. BAPTA partially reduced phenylephrine-induced enhancement of ET-1 and ROS, suggesting that α1 receptor activation can enhance ROS/ET-1 generation in both calcium-dependent and calcium-independent ways.</p><p>The study demonstrates that high concentration catecholamine can activate SK1–3 channels through α1 receptor-ROS signalling and increase ET-1 production, facilitating vasoconstriction.</p></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"155 ","pages":"Article 104699"},"PeriodicalIF":2.9,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0026286224000487/pdfft?md5=5a77f3e9f848d1582231b15caec297a0&pid=1-s2.0-S0026286224000487-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rodrigo Viana , Larissa Joaquim , Fabrício Weinheimer Lippert , Naila Maciel Andrade , Nathalia Carvalho Fleith , Carla Damasio , Anita Tiscoski , David dos Santos , Richard Simon Machado , Lucineia Gainski Danielski , Khiany Mathias , Solange Stork , Gabriela Bernardes , Yasmin Strickert , Carlos Henrique Perin , Wendel Dietzi , Sandra Bonfante , Pedro Bitencourt , Lucas Felacio , Jucelia Jeremias Fortunato , Fabricia Petronilho
{"title":"Sepsis after middle cerebral artery occlusion exacerbates peripheral oxidative stress in a sex-specific manner","authors":"Rodrigo Viana , Larissa Joaquim , Fabrício Weinheimer Lippert , Naila Maciel Andrade , Nathalia Carvalho Fleith , Carla Damasio , Anita Tiscoski , David dos Santos , Richard Simon Machado , Lucineia Gainski Danielski , Khiany Mathias , Solange Stork , Gabriela Bernardes , Yasmin Strickert , Carlos Henrique Perin , Wendel Dietzi , Sandra Bonfante , Pedro Bitencourt , Lucas Felacio , Jucelia Jeremias Fortunato , Fabricia Petronilho","doi":"10.1016/j.mvr.2024.104711","DOIUrl":"10.1016/j.mvr.2024.104711","url":null,"abstract":"<div><p>Ischemic stroke occurs due a blockage in the blood flow to the brain, leading to damage to the nervous system. The prevalent morbidities resulting from stroke include post-stroke infection, as sepsis. Additionally, oxidative stress is recognized for inducing functional deficits in peripheral organs during sepsis. Therefore, sex differences in stroke exist and we aimed to investigate the peripheral oxidative stress caused by sepsis after stroke in male and female rats. Wistar rats (male and female) were divided into sham+sham, middle cerebral artery occlusion (MCAO) + sham, sham+ cecal ligation and perforation (CLP) and MCAO+CLP groups to males and female rats. Animals were subjected to MCAO or sham and after 7 days, were subjected to sepsis by CLP or sham. After 24 h, serum, total brain, lung, liver, heart, and spleen were collected. Brain edema, myeloperoxidase (MPO) activity, nitrite/nitrate (N/N) concentration, oxidative damage to lipids and proteins, and catalase activity were evaluated. Brain edema was observed only in male rats in MCAO+CLP group compared to MCAO+sham. Regarding MPO activity, an increase was verified in male in different organs and serum in MCAO+CLP group. For N/N levels, the increase was more pronounced in females submitted to MCAO+CLP. In general, to oxidative stress, an increase was only observed in animals exposed to MCAO+CLP, or with a greater increase in this group compared to the others. The findings provided the first indication that animals exposed to MCAO exhibit a heightened vulnerability to the harmful impacts of sepsis, as evidenced by brain edema and peripheral oxidative stress, and this susceptibility is dependent of sex.</p></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"155 ","pages":"Article 104711"},"PeriodicalIF":2.9,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Vincristine attenuates isoprenaline-induced cardiac hypertrophy in male Wistar rats via suppression of ROS/NO/NF-қB signalling pathways","authors":"Jerome Ndudi Asiwe , Abayomi M. Ajayi , Benneth Ben-Azu , Adesoji Adedipe Fasanmade","doi":"10.1016/j.mvr.2024.104710","DOIUrl":"10.1016/j.mvr.2024.104710","url":null,"abstract":"<div><p>Vincristine (VCR), a vinca alkaloid with anti-tumor and anti-oxidant properties, is acclaimed to possess cardioprotective action. However, the molecular mechanism underlying this protective effect remains unknown. This study investigated the effects of VCR on isoprenaline (ISO), a beta-adrenergic receptor agonist, induced cardiac hypertrophy in male Wistar rats. Animals were pre-treated with ISO (1 mg/kg) intraperitoneally for 14 days before VCR (25 μg/kg) intraperitoneal injection from days 1 to 28. Thereafter, mechanical, and electrical activities of the hearts of the rats were measured using a non-invasive blood pressure monitor and an electrocardiograph, respectively. After which, the heart was homogenized, and supernatants were assayed for contractile proteins: endothelin-1, cardiac troponin-1, angiotensin-II, and creatine kinase-MB, with markers of oxidative/nitrergic stress (SOD, CAT, MDA, GSH, and NO), inflammation (TNF-a and IL-6, NF-kB), and caspase-3 indicative of VCR reduced elevated blood pressure and reversed the abnormal electrocardiogram. ISO-induced increased endothelin-1, cardiac troponin-1, angiotensin-II, and creatine phosphokinase-MB, which were reversed by VCR. ISO also increased TNF-α, IL-6, NF-kB expression with increased caspase-3-mediated apoptosis in the heart. However, VCR reduced ISO-induced inflammation and apoptosis, with improved endogenous antioxidant agents (GSH, SOD, CAT) relative to ISO controls. Moreso, VCR, protected against ISO-induced histoarchitectural degeneration of cardiac myofibre. The result of this study revealed that VCR treatment significantly reverses ISO-induced cardiac hypertrophic phenotypes, via mechanisms connected to improved levels of proteins involved in excitation-contraction, and suppression of oxido-inflammatory and apoptotic pathways.</p></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"155 ","pages":"Article 104710"},"PeriodicalIF":3.1,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marissa N. Baranauskas , Tyler H. Blechschmid , Emily B. Long , Andrew R. Coggan , Stephen J. Carter
{"title":"Dietary NO3− does not enhance endothelial dependent cutaneous vascular conductance in older women","authors":"Marissa N. Baranauskas , Tyler H. Blechschmid , Emily B. Long , Andrew R. Coggan , Stephen J. Carter","doi":"10.1016/j.mvr.2024.104706","DOIUrl":"10.1016/j.mvr.2024.104706","url":null,"abstract":"<div><p>Prior work has yet to determine whether the reduction of dietary nitrate (NO<sub>3</sub><sup>−</sup>) to NO, via the enterosalivary pathway, may modify cutaneous vascular conductance (CVC) responses to local heating in older women. Changes occurring with the transition to menopause related to hormonal flux, increased adiposity, and/or decreased physical activity may further compound the negative influence of aging on nitric oxide (NO)-dependent CVC. Herein, we characterized changes in NO-dependent CVC following acute ingestion of 140 mL of NO<sub>3</sub><sup>−</sup>-rich beetroot juice in 24 older women (age: 65 ± 5 y, BMI: 31.2 ± 3.7 kg/m<sup>2</sup>). Red blood cell (RBC) flux was measured continuously via laser-Doppler flowmetry on the dorsal aspect of the forearm during local skin heating to 39 °C/44 °C before and 3 h after NO<sub>3</sub><sup>−</sup> ingestion. NO-dependent changes in CVC were calculated as RBC flux/mean arterial blood pressure at 39 °C and normalized as a proportion of maximal CVC at 44 °C (%CVCmax). Changes (Δ) in fractional exhaled NO (FeNO) following NO<sub>3</sub><sup>−</sup> ingestion were used an index of NO bioavailability. Despite increased FeNO (+81 ± 70 %, <em>P</em> < 0.001), %CVCmax at 39 °C was reduced (−16 ± 10 %, <em>P</em> < 0.001) following NO<sub>3</sub><sup>−</sup> ingestion. A greater reduction in %CVCmax was weakly to moderately associated with higher body fat% (<em>r</em> = 0.45 [0.05–0.72], <em>P</em> = 0.029), central adiposity% (<em>r</em> = 0.50 [0.13–0.75], <em>P</em> = 0.012), neutrophil% (<em>r</em> = 0.42 [0.02–0.70], <em>P</em> = 0.041), and higher neutrophil to lymphocyte ratio (<em>r</em> = 0.49 [0.11–0.75], <em>P</em> = 0.016). These findings demonstrate a single dose of dietary NO<sub>3</sub><sup>−</sup> does not promote CVC responses to local heating in sedentary older women with overweight and obesity. Correlation with multiple biomarkers suggest systemic inflammation may be involved.</p></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"155 ","pages":"Article 104706"},"PeriodicalIF":3.1,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}