Microcirculation最新文献

{"title":"Serine proteases mediate leukocyte recruitment and hepatic microvascular injury in the acute phase following extended hepatectomy","authors":"Yunjie Zhang,&nbsp;Patrick Huber,&nbsp;Marc Praetner,&nbsp;Alice Zöllner,&nbsp;Lesca Holdt,&nbsp;Andrej Khandoga,&nbsp;Maximilian Lerchenberger","doi":"10.1111/micc.12796","DOIUrl":"10.1111/micc.12796","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Post-hepatectomy liver failure (PHLF) is the main limitation of extended liver resection. The molecular mechanism and the role of leukocytes in the development of PHLF remain to be unveiled. We aimed to address the impact of serine proteases (SPs) on the acute phase after liver resection by intravitally analyzing leukocyte recruitment and changes in hemodynamics and microcirculation of the liver.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>C57BL/6 mice undergoing 60% partial hepatectomy were treated with aprotinin (broad-spectrum SP inhibitor), tranexamic acid (plasmin inhibitor), or vehicle. Sham-operated animals served as controls. In vivo fluorescence microscopy was used to quantify leukocyte-endothelial interactions immediately after, as well as 120 min after partial hepatectomy in postsinusoidal venules, along with measurement of sinusoidal perfusion rate and postsinusoidal shear rate. Recruitment of leukocytes, neutrophils, T cells, and parameters of liver injury were assessed in tissue/blood samples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Leukocyte recruitment, sinusoidal perfusion failure rate, and shear rate were significantly increased in mice after 60% partial hepatectomy compared to sham-operated animals. The inhibition of SPs or plasmin significantly attenuated leukocyte recruitment and improved the perfusion rate in the remnant liver. ICAM-1 expression and neutrophil recruitment significantly increased after 60% partial hepatectomy and were strongly reduced by plasmin inhibition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Endothelial activation and leukocyte recruitment in the liver in response to the increment of sinusoidal shear rate were hallmarks in the acute phase after liver resection. SPs mediated leukocyte recruitment and contributed to the impairment of sinusoidal perfusion in an ICAM-1-dependent manner in the acute phase after liver resection.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12796","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10609667","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":"KIR channel regulation of electrical conduction along cerebrovascular endothelium: Enhanced modulation during Alzheimer's disease","authors":"Md A. Hakim,&nbsp;Erik J. Behringer","doi":"10.1111/micc.12797","DOIUrl":"https://doi.org/10.1111/micc.12797","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Endothelial cell (EC) coupling occurs through gap junctions and underlies cerebral blood flow regulation governed by inward-rectifying K⁺ (K_IR) channels. This study addressed effects of K_IR channel activity on EC coupling before and during Alzheimer's disease (AD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Intact EC tubes (width: ~90–100 μm; length: ~0.5 mm) were freshly isolated from posterior cerebral arteries of young Pre-AD (1–3 months) and aged AD (13–18 months) male and female <i>3xTg-AD</i> mice. Dual intracellular microelectrodes applied simultaneous current injections (±0.5–3 nA) and membrane potential (V_m) recordings in ECs at distance ~400 μm. Elevated extracellular potassium ([K⁺]_E; 8–15 mmol/L; reference, 5 mmol/L) activated K_IR channels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Conducted V_m (∆V_m) responses ranged from ~−30 to 30 mV in response to −3 to +3 nA (linear regression, <i>R</i>² ≥ .99) while lacking rectification for charge polarity or axial direction of spread. Conduction slope decreased ~10%–20% during 15 mmol/L [K⁺]_E in Pre-AD males and AD females. 15 mmol/L [K⁺]_E decreased conduction by ~10%–20% at lower ∆V_m thresholds in AD animals (~±20 mV) versus Pre-AD (~±25 mV). AD increased conducted hyperpolarization by ~10%–15% during 8–12 mmol/L [K⁺]_E.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Brain endothelial K_IR channel activity modulates bidirectional spread of vasoreactive signals with enhanced regulation of EC coupling during AD pathology.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12797","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50146429","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":"Comparison of laser speckle contrast imaging with laser Doppler perfusion imaging for tissue perfusion measurement","authors":"Goksel Guven,&nbsp;Annemieke Dijkstra,&nbsp;Tjallingius Martijn Kuijper,&nbsp;Nicole Trommel,&nbsp;Margriet Elisabeth van Baar,&nbsp;Arzu Topeli,&nbsp;Can Ince,&nbsp;Cornelis Hendrik van der Vlies","doi":"10.1111/micc.12795","DOIUrl":"10.1111/micc.12795","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Laser-based tissue perfusion monitoring techniques have been increasingly used in animal and human research to assess blood flow. However, these techniques use arbitrary units, and knowledge about their comparability is scarce. This study aimed to model the relationship between laser speckle contrast imaging (LSCI) and laser Doppler perfusion imaging (LDPI), for measuring tissue perfusion over a wide range of blood flux values.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Fifteen healthy volunteers (53% female, median age 29 [IQR 22–40] years) were enrolled in this study. We performed iontophoresis with sodium nitroprusside on the forearm to induce regional vasodilation to increase skin blood flux. Besides, a stepwise vascular occlusion was applied on the contralateral upper arm to reduce blood flux. Both techniques were compared using a linear mixed model analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Baseline blood flux values measured by LSCI were 33 ± 6.5 arbitrary unit (AU) (Coefficient of variation [CV] = 20%) and by LDPI 60 ± 11.5 AU (CV = 19%). At the end of the iontophoresis protocol, the regional blood flux increased to 724 ± 412% and 259 ± 87% of baseline measured by LDPI and LSCI, respectively. On the other hand, during the stepwise vascular occlusion test, the blood flux reduced to 212 ± 40% and 412 ± 177% of its baseline at LDPI and LSCI, respectively. A strong correlation was found between the LSCI and LDPI instruments at increased blood flux with respect to baseline skin blood flux; however, the correlation was weak at reduced blood flux with respect to baseline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>LSCI and LDPI instruments are highly linear for blood flux higher than baseline skin blood flux; however, the correlation decreased for blood flux lower than baseline. This study's findings could be a basis for using LSCI in specific patient populations, such as burn care.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7f/de/MICC-30-0.PMC10078364.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9267280","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":"Impairment of endothelial progenitor cells in women after kidney transplantation","authors":"Nadia Meyer,&nbsp;Katja Richter,&nbsp;Lars Brodowski,&nbsp;Constantin von Kaisenberg,&nbsp;Anette Melk,&nbsp;Bernhard Schmidt,&nbsp;Florian P. Limbourg,&nbsp;Bianca Schröder-Heurich,&nbsp;Frauke von Versen-Höynck","doi":"10.1111/micc.12794","DOIUrl":"10.1111/micc.12794","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The long-term survival of kidney transplant patients has substantially improved. However, there is a higher risk for cardiovascular events after transplantation, partly due to immunosuppression. A diminished number of endothelial progenitor cells (EPCs), which play an important role in angiogenesis and the repair of endothelial damage, are associated with an increased cardiovascular risk. The aim of this study was to evaluate whether kidney transplantation affects EPCs in women.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Twenty-four healthy women and 22 female kidney transplant recipients were recruited. The ratio of angiogenic and non-angiogenic circulating progenitor cells (CPCs) was determined by multicolor flow cytometry and related to clinical parameters. Cord blood-derived endothelial colony-forming cells (ECFCs), a proliferative subgroup of endothelial progenitor cells, were treated with pooled sera from transplant patients or healthy controls and tested for their functional integrity using in vitro models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Kidney transplant recipients displayed a reduced ratio of angiogenic and non-angiogenic CPCs compared to healthy controls. Differences were especially pronounced in premenopausal women. Exposure to sera of transplanted women led to a significant impairment of ECFC proliferation, migration, and angiogenesis ability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Alterations of EPC populations may contribute to the higher cardiovascular risks after organ transplantation and should be considered in therapeutic strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12794","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10602334","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":"Engineered models of the lymphatic vascular system: Past, present, and future","authors":"Amirali Selahi,&nbsp;Abhishek Jain","doi":"10.1111/micc.12793","DOIUrl":"10.1111/micc.12793","url":null,"abstract":"<p>The lymphatic vascular system is crucial for optimizing body fluid level, regulating immune function, and transporting lipid. Relative to the experimental models to investigate blood vasculature, there are significantly fewer tools to explore lymphatics. Although in vivo studies have contributed to major discoveries in the field, finding and characterizing lymphatic specific markers has opened the door to isolating lymphatic vessels and cells for building ex vivo and in vitro platforms. These preparations have enabled the study and analysis of lymphatic vasculature in various physiological and pathophysiological conditions leading to a better understanding of cellular expressions and signaling. In this review, a broad range of ex vivo and in vitro engineered models are highlighted and categorized based on the major lymphatic function they model including contractile function, inflammation, drainage and immune regulation, lymphangiogenesis, and tumor-lymphatic interactions. Then, the novel 3D engineered tissues are introduced consisting of acellularized scaffolds and hydrogels to form vessels and cellular structures close to in vivo morphology. This paper also compares traditional in vitro methods with recent technologies and elaborates on the inherent advantages and limitations of each preparation by critically discussing simplest to most complex tissue-cellular structures. It concludes with an outlook of the lymphatic vasculature models and the possible future direction of contemporary tools, such as organ-on-chips.</p>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 2-3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9427243","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":"Abstracts from the 47th Annual Meeting of Japanese Society for Microcirculation","authors":"","doi":"10.1111/micc.12784","DOIUrl":"10.1111/micc.12784","url":null,"abstract":"We aneurysms based the in vascular endothelial cells triggers aneurysm development. Methods : We investigated the role of P2X4 purinoceptor, which is involved in flow- sensitive mechanisms in vascular endothelial cells, in the development of cerebral aneurysms by using the aneurysm-induced animal model. We also prospectively enrolled human patients with unruptured cerebral aneurysms, observed them for 3 years with cerebrovascular 3D imaging and carotid artery echo -cardiography, and compared the hemodynamic environments of the growth group with those of the non- growth group using computa-tional fluid dynamics (CFD) technique. Results : The incidence of cerebral aneurysms in aneurysm- induced P2X4 (−/−) mice was significantly lower than that in P2X4 (+/+) mice, and the incidence of cerebral aneurysms in aneurysm- induced rats treated with a P2X4 inhibitor, paroxetine was significantly lower than that in the non- treated group. Paroxetine treatment also significantly suppressed aneurysm growth. In the clinical study of human unruptured cerebral aneurysms, 461 patients were enrolled, and during the 3- year observation period, 38 aneurysms enlarged and 209 ones did not. In the CFD analysis, the magnitude of wall shear stress and transWSS, a metrics for shear stress disturbance, was significantly increased in the enlarged group, especially in the aneurysm neck. Normal brain function depends on stable cerebral blood flow and cerebral autoregulation. Cerebral blood flow is maintained even when blood pressure fluctuates. However, microcirculation in the cortex is not well understood when blood pressure drops rapidly. The purpose of this study was to determine oxyhemoglobin (O 2 Hb) changes, the indicator of cortical blood flow changes, during hypotension induced by thigh cuff release. Ten healthy students participated in this study. They were seated in a recumbent position in a quiet room. The cuffs of digital tourniquets were placed on both thighs and inflated to 250 mmHg for 5 min after 5 min rest, followed by deflation for 5 min. Right (R- ) and left (L- ) prefrontal cortex (PFC) O 2 Hb levels were measured using a multi- channel near- infrared spectroscopy system (LABNIRS; Shimadzu Co). O 2 Hb levels for each area were measured. Beat- to- beat mean arterial pressure (MAP) was recorded by volume clamping the finger pulse with a finger photoplethysmograph (Finometer; Finapres Medical Systems) on the left middle finger. O 2 Hb and MAP were averaged 1- sec epoch throughout the experi-ment. This study was approved by the Ethics Committee of Niigata University of Health and Welfare (18649- 210618). The decrease in MAP after the cuff release was 31.3 ± 5.6 mmHg. The decrease in O 2 Hb levels in the L- PFC (0.196 ± 0.088 mM∙cm) was larger than that in R- PFC (0.165 ± 0.072 mM∙cm) ( p &lt; .05). These results suggest that the effect of hypotension induced by thigh cuff release on cortical blood flow might be different between cortical regions. Background : Pers","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"29 8","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10438153","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":"Lentiviral overexpression of VEGFC in transplanted MSCs leads to resolution of swelling in a mouse tail lymphedema model","authors":"Eleftheria Michalaki,&nbsp;Josephine M. Rudd,&nbsp;Lauren Liebman,&nbsp;Rahul Wadhwani,&nbsp;Levi B. Wood,&nbsp;Nick J. Willett,&nbsp;J. Brandon Dixon","doi":"10.1111/micc.12792","DOIUrl":"10.1111/micc.12792","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Dysfunction of the lymphatic system following injury, disease, or cancer treatment can lead to lymphedema, a debilitating condition with no cure. Despite the various physical therapy and surgical options available, most treatments are palliative and fail to address the underlying lymphatic vascular insufficiency driving lymphedema progression. Stem cell therapy provides a promising alternative in the treatment of various chronic diseases with a wide range of therapeutic effects that reduce inflammation, fibrosis, and oxidative stress, while promoting lymphatic vessel (LV) regeneration. Specifically, stem cell transplantation is suggested to promote LV restoration, rebuild lymphatic circulation, and thus potentially be utilized towards an effective lymphedema treatment. In addition to stem cells, studies have proposed the administration of vascular endothelial growth factor C (VEGFC) to promote lymphangiogenesis and decrease swelling in lymphedema.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Here, we seek to combine the benefits of stem cell therapy, which provides a cellular therapeutic approach that can respond to the tissue environment, and VEGFC administration to restore lymphatic drainage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials &amp; Methods</h3>\u0000 \u0000 <p>Specifically, we engineered mesenchymal stem cells (MSCs) to overexpress VEGFC using a lentiviral vector (hVEGFC MSC) and investigated their therapeutic efficacy in improving LV function and tissue swelling using near infrared (NIR) imaging, and lymphatic regeneration in a single LV ligation mouse tail lymphedema model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>First, we showed that overexpression of VEGFC using lentiviral transduction led to an increase in VEGFC protein synthesis in vitro. Then, we demonstrated hVEGFC MSC administration post-injury significantly increased the lymphatic contraction frequency 14-, 21-, and 28-days post-surgery compared to the control animals (MSC administration) in vivo, while also reducing tail swelling 28-days post-surgery compared to controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our results suggest a therapeutic potential of hVEGFC MSC in alleviating the lymphatic dysfunction observed during lymphedema progression after secondary injury and could provide a promising approach to enhancing autologous cell therapy for treating lymphedema.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 2-3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9803358","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":"GATA2 regulates blood/lymph separation in a platelet-dependent and lymphovenous valve-independent manner","authors":"Md. Riaj Mahamud,&nbsp;Xin Geng,&nbsp;Lijuan Chen,&nbsp;Zoheb Ahmed,&nbsp;Yenchun Ho,&nbsp;R. Sathish Srinivasan","doi":"10.1111/micc.12787","DOIUrl":"10.1111/micc.12787","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Lymphatic vessels collect interstitial fluid, immune cells, and digested lipids and return these bodily fluids to blood through two pairs of lymphovenous valves (LVVs). Like other cardiovascular valves LVVs prevent the backflow of blood into the lymphatic vessels. In addition to LVVs, platelets are necessary to prevent the entry of blood into the lymphatic vessels. Platelet thrombi are observed at LVVs suggesting that LVVs and platelets function in synergy to regulate blood/lymphatic separation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The primary objective of this work is to determine whether platelets can regulate blood/lymph separation independently of LVVs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The transcription factor GATA2 is necessary for the development of both LVVs and hematopoietic stem cells. Using various endothelial- and hematopoietic cell expressed Cre-lines, we conditionally deleted Gata2. We hypothesized that this strategy would identify the tissue- and time-specific roles of GATA2 and reveal whether platelets and LVVs can independently regulate blood/lymph separation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Lymphatic vasculature-specific deletion of Gata2 results in the absence of LVVs without compromising blood/lymph separation. In contrast, deletion of GATA2 from both lymphatic vasculature and hematopoietic cells results in the absence of LVVs, reduced number of platelets and blood-filled lymphatic vasculature.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>GATA2 promotes blood/lymph separation through platelets. Furthermore, LVVs are the only known sites of interaction between blood and lymphatic vessels. The fact that blood is able to enter the lymphatic vessels of mice lacking LVVs and platelets indicates that under these circumstances the lymphatic and blood vessels are connected at yet to be identified sites.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 2-3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12787","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9489317","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":"RNA-seq profiling reveals different pathways between remodeled vessels and myocardium in hypertrophic cardiomyopathy","authors":"Annalinda Pisano,&nbsp;Loredana Le Pera,&nbsp;Raffaella Carletti,&nbsp;Bruna Cerbelli,&nbsp;Maria G. Pignataro,&nbsp;Angelina Pernazza,&nbsp;Fabrizio Ferre,&nbsp;Maria Lombardi,&nbsp;Davide Lazzeroni,&nbsp;Iacopo Olivotto,&nbsp;Ornella E. Rimoldi,&nbsp;Chiara Foglieni,&nbsp;Paolo G. Camici,&nbsp;Giulia d'Amati","doi":"10.1111/micc.12790","DOIUrl":"10.1111/micc.12790","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Coronary microvascular dysfunction (CMD) is a key pathophysiological feature of hypertrophic cardiomyopathy (HCM), contributing to myocardial ischemia and representing a critical determinant of patients' adverse outcome. The molecular mechanisms underlying the morphological and functional changes of CMD are still unknown. Aim of this study was to obtain insights on the molecular pathways associated with microvessel remodeling in HCM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Interventricular septum myectomies from patients with obstructive HCM (<i>n</i> = 20) and donors' hearts (CTRL, discarded for technical reasons, <i>n</i> = 7) were collected. Remodeled intramyocardial arterioles and cardiomyocytes were microdissected by laser capture and next-generation sequencing was used to delineate the transcriptome profile.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 720 exclusive differentially expressed genes (DEGs) in cardiomyocytes and 1315 exclusive DEGs in remodeled arterioles of HCM. Performing gene ontology and pathway enrichment analyses, we identified selectively altered pathways between remodeled arterioles and cardiomyocytes in HCM patients and controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We demonstrate the existence of distinctive pathways between remodeled arterioles and cardiomyocytes in HCM patients and controls at the transcriptome level.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"29 8","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9787970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10447526","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":"Impact of Goreisan components on rat mesenteric collecting lymphatic vessel pumping","authors":"Michiko Jo,&nbsp;Andrea N. Trujillo,&nbsp;Naotoshi Shibahara,&nbsp;Jerome W. Breslin","doi":"10.1111/micc.12788","DOIUrl":"10.1111/micc.12788","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Goreisan is a traditional herbal formulation with diuretic properties tested as a clinical therapeutic to alleviate lymphedema in Japan. The present study aimed to determine how Goreisan and its five different components affect lymphatic pump function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Mesenteric collecting lymphatics were isolated from anesthetized Sprague–Dawley rats and mounted on resistance-matched glass micropipettes in a 37°C physiological salt solution bath for studies. Diameter was continuously measured to obtain the following lymphatic pump parameters: contraction frequency (CF), end diastolic diameter (EDD), and end systolic diameter (ESD), contraction amplitude (AMP), ejection fraction (EF), and fractional pump flow (FPF). Goreisan and each of its components (Cinnamomi Cortex, Atractylodis Rhizoma, Alismatis Rhizoma, Polyporus, and Poria) were applied to the bath at concentrations of 1–30 μg/mL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results show that while Goreisan causes no significant changes to lymphatic pumping, Alismatis Rhizoma and Polyporus each significantly reduce CF and FPF. In addition, rats that received oral administration of Goreisan and Alismatis Rhizoma for 1 week had elevated expression of VEGFR-3 in their mesenteric collecting lymphatics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Collectively, the results suggest that some components of Goreisan have a direct, rapid impact on lymphatic pumping. These findings provide new insights but also raise new questions about the therapeutic potential of Goreisan in patients with secondary lymphedema.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 2-3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12788","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9803328","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}