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1.
Nat Commun ; 10(1): 4091, 2019 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-31501425

RESUMO

Organisms rely upon external cues to avoid detrimental conditions during environmental change. Rapid water loss, or desiccation, is a universal threat for terrestrial plants and animals, especially under climate change, but the cues that facilitate plastic responses to avoid desiccation are unclear. We integrate acclimation experiments with gene expression analyses to identify the cues that regulate resistance to water loss at the physiological and regulatory level in a montane salamander (Plethodon metcalfi). Here we show that temperature is an important cue for developing a desiccation-resistant phenotype and might act as a reliable cue for organisms across the globe. Gene expression analyses consistently identify regulation of stem cell differentiation and embryonic development of vasculature. The temperature-sensitive blood vessel development suggests that salamanders regulate water loss through the regression and regeneration of capillary beds in the skin, indicating that tissue regeneration may be used for physiological purposes beyond replacing lost limbs.


Assuntos
Mudança Climática , Sinais (Psicologia) , Dessecação , Temperatura Ambiente , Urodelos/fisiologia , Animais , Vasos Sanguíneos/crescimento & desenvolvimento , Vasos Sanguíneos/metabolismo , Redes Reguladoras de Genes , Lipídeos/química , Neovascularização Fisiológica/genética , Fatores de Risco , Pele , Transcrição Genética , Transcriptoma/genética , Urodelos/genética
3.
Kidney Blood Press Res ; 44(4): 643-655, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31430759

RESUMO

AIMS: The current study was conducted with the central objective of investigating the expression of microRNA-145 (miR-145) in renal vascular lesions (RVLs) in juvenile lupus nephritis (JLN) and its possible mechanism. METHODS: The clinical data of 49 JLN patients confirmed by renal biopsy were collected and followed by grouping according to the RVLs score after hematoxylin-eosin staining: mild, moderate, and severe groups. In situ hybridization was used to detect the expression of miR-145 in renal vessels which was then being compared among different RVLs groups. Up-LV-miR-145 and LV-miR-NC lentiviral vectors were constructed and transfected into human vascular smooth muscle cells (HVSMCs), respectively. After HVSMCs were treated with 10.0 µg/L platelet-derived growth factor (PDGF)-BB for 24 h, the proliferation, migration, and apoptosis of endothelial cells were detected by MTT, Transwell assay, and flow cytometry, respectively. Western blot was used to detect expression of alpha-smooth muscle actin (α-SM-actin) and osteopontin (OPN). RESULTS: The expression of miR-145 in renal vascular cells was statistically significant. The higher the inner membrane ratio, the lesser the miR-145 expression. After treatment with PDGF-BB, expression of miR-145 in HVSMCs decreased, proliferation and migration ability enhanced, apoptosis decreased, α-SM-actin decreased, and OPN increased. The proliferation and migration ability of HVSMCs in the LV-miR-145 group suppressed, apoptosis enhanced, α-SM-actin increased, and OPN decreased. CONCLUSIONS: Our study revealed that miR-145 expression decreased with the increase of vascular damage. miR-145 can inhibit proliferation, migration, and differentiation phenotypic transformation of HVSMCs induced by PDGF-BB. miR-145 may be involved in the pathogenesis of RVLs and may be a new target for treatment of RVLs in lupus nephritis.


Assuntos
Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/patologia , MicroRNAs/farmacologia , Adolescente , Apoptose/efeitos dos fármacos , Becaplermina/farmacologia , Vasos Sanguíneos/citologia , Vasos Sanguíneos/metabolismo , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Criança , Pré-Escolar , Feminino , Humanos , Rim/irrigação sanguínea , Nefrite Lúpica/etiologia , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Transfecção
4.
Opt Lett ; 44(15): 3773-3776, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31368965

RESUMO

Hypoxia, a low tissue oxygenation condition caused by insufficient oxygen supply, leads to potentially irreversible tissue damage, such as brain infarction during stroke. Intravascular oxygenation has long been used by photoacoustic imaging, among other imaging modalities, to study hypoxia. However, intravascular oxygenation describes only the oxygen supply via microcirculation, which does not directly reflect the amount of free oxygen available for metabolism in the interstitial fluid. Therefore, to fully understand hypoxia, it is highly desirable to monitor blood oxygenation as well as tissue oxygenation during the same biological process. In this work, by combining high-resolution photoacoustic microscopy (PAM) and a novel bioreducible N-oxide-based hypoxia-sensitive probe HyP-650, we have demonstrated simultaneous imaging of intravascular oxygenation and tissue hypoxia. We have established detailed chemical, optical, and photoacoustic properties of HyP-650 for hypoxic activation in vitro and in living cells. We have also performed PAM on hindlimb ischemia models and tumor-bearing mice to study the correlation between intravascular oxygenation and tissue oxygenation at various hypoxic levels. We expect that Hyp-650 enhanced photoacoustic imaging will find a variety of applications in brain and cancer research.


Assuntos
Vasos Sanguíneos/diagnóstico por imagem , Vasos Sanguíneos/metabolismo , Oxigênio/metabolismo , Técnicas Fotoacústicas/métodos , Animais , Membro Posterior/irrigação sanguínea , Isquemia/metabolismo , Isquemia/patologia , Camundongos , Microscopia , Hipóxia Tumoral
5.
Int J Mol Sci ; 20(15)2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31344780

RESUMO

Collaterals are unique blood vessels present in the microcirculation of most tissues that, by cross-connecting a small fraction of the outer branches of adjacent arterial trees, provide alternate routes of perfusion. However, collaterals are especially susceptible to rarefaction caused by aging, other vascular risk factors, and mouse models of Alzheimer's disease-a vulnerability attributed to the disturbed hemodynamic environment in the watershed regions where they reside. We examined the hypothesis that endothelial and smooth muscle cells (ECs and SMCs, respectively) of collaterals have specializations, distinct from those of similarly-sized nearby distal-most arterioles (DMAs) that maintain collateral integrity despite their continuous exposure to low and oscillatory/disturbed shear stress, high wall stress, and low blood oxygen. Examination of mouse brain revealed the following: Unlike the pro-inflammatory cobble-stoned morphology of ECs exposed to low/oscillatory shear stress elsewhere in the vasculature, collateral ECs are aligned with the vessel axis. Primary cilia, which sense shear stress, are present, unexpectedly, on ECs of collaterals and DMAs but are less abundant on collaterals. Unlike DMAs, collaterals are continuously invested with SMCs, have increased expression of Pycard, Ki67, Pdgfb, Angpt2, Dll4, Ephrinb2, and eNOS, and maintain expression of Klf2/4. Collaterals lack tortuosity when first formed during development, but tortuosity becomes evident within days after birth, progresses through middle age, and then declines-results consistent with the concept that collateral wall cells have a higher turnover rate than DMAs that favors proliferative senescence and collateral rarefaction. In conclusion, endothelial and SMCs of collaterals have morphologic and functional differences from those of nearby similarly sized arterioles. Future studies are required to determine if they represent specializations that counterbalance the disturbed hemodynamic, pro-inflammatory, and pro-proliferative environment in which collaterals reside and thus mitigate their risk factor-induced rarefaction.


Assuntos
Vasos Sanguíneos/metabolismo , Circulação Colateral/genética , Miócitos de Músculo Liso/metabolismo , Neovascularização Fisiológica/genética , Envelhecimento/genética , Envelhecimento/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Animais , Vasos Sanguíneos/patologia , Circulação Colateral/fisiologia , Células Endoteliais/metabolismo , Artéria Femoral/crescimento & desenvolvimento , Artéria Femoral/metabolismo , Membro Posterior/irrigação sanguínea , Humanos , Camundongos , Fatores de Risco , Transdução de Sinais
6.
Immunity ; 51(1): 90-103.e3, 2019 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-31278057

RESUMO

The key sites within the gastrointestinal (GI) tract where T cells mediate effector responses and the impact of these responses on intestinal stem cells (ISCs) remain unclear. Using experimental bone marrow transplantation to model immune-mediated GI damage and 3D imaging to analyze T cell localization, we found that the ISC compartment is the primary intestinal site targeted by T cells after transplantation. Recruitment to the crypt base region resulted in direct T cell engagement with the stem cell compartment and loss of crypt base columnar ISCs, which expressed both MHC classes I and II. Vasculature expressing the adhesion molecule MAdCAM-1 clustered near the crypt base, preferentially regulating crypt compartment invasion and ISC reduction without affecting T cell migration to villi. These findings indicate that allogeneic T cells rapidly access the stem cell niche after transplantation, and this targeted recruitment to the stem cell compartment results in ISC loss during immune-mediated GI damage.


Assuntos
Células-Tronco Adultas/imunologia , Transplante de Medula Óssea , Mucosa Intestinal/imunologia , Nicho de Células-Tronco/imunologia , Linfócitos T/imunologia , Animais , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/patologia , Moléculas de Adesão Celular/metabolismo , Movimento Celular , Citotoxicidade Imunológica , Feminino , Humanos , Imagem Tridimensional , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Pessoa de Meia-Idade , Modelos Animais , Transplante Homólogo
7.
Life Sci ; 232: 116651, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31302195

RESUMO

The miR-19 family, including miR-19a, miR-19b-1 and miR-19b-2, arises from two different paralogous clusters miR-17-92 and miR-106a-363. Although it is identified as oncogenic miRNA, the miR-19 family has also been found to play important roles in regulating normal tissue development. The precise control of miR-19 family level is essential for keeping tissue homeostasis and normal development of organisms. Its dysregulation leads to dysplasia, disease and even cancer. Therefore, this review focuses on the roles of miR-19 family in the development and disease of heart, vessels and neurons to estimate the potential value of miR-19 family as diagnostic biomarker or therapeutic target of cardiac, neurological, and vascular diseases.


Assuntos
Vasos Sanguíneos/metabolismo , MicroRNAs/genética , Miocárdio/metabolismo , Neurônios/metabolismo , Biomarcadores/metabolismo , Humanos
8.
Cells ; 8(6)2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-31174284

RESUMO

Blood vessels are required for the survival of any organism larger than the oxygen diffusion limit. Blood vessel formation is a tightly regulated event and vessel growth or changes in permeability are linked to a number of diseases. Elucidating the cell biology of endothelial cells (ECs), which are the building blocks of blood vessels, is thus critical to our understanding of vascular biology and to the development of vascular-targeted disease treatments. Small GTPases of the Rho GTPase family are known to regulate several processes critical for EC growth and maintenance. In fact, many of the 21 Rho GTPases in mammals are known to regulate EC junctional remodeling, cell shape changes, and other processes. Rho GTPases are thus an attractive target for disease treatments, as they often have unique functions in specific vascular cell types. In fact, some Rho GTPases are even expressed with relative specificity in diseased vessels. Interestingly, many Rho GTPases are understudied in ECs, despite their known expression in either developing or mature vessels, suggesting an even greater wealth of knowledge yet to be gleaned from these complex signaling pathways. This review aims to provide an overview of Rho GTPase signaling contributions to EC vasculogenesis, angiogenesis, and mature vessel barrier function. A particular emphasis is placed on so-called "alternative" Rho GTPases, as they are largely understudied despite their likely important contributions to EC biology.


Assuntos
Vasos Sanguíneos/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo , Animais , Adesão Celular , Hemangioma Cavernoso do Sistema Nervoso Central/metabolismo , Hemangioma Cavernoso do Sistema Nervoso Central/patologia , Humanos , Neoplasias/irrigação sanguínea , Neoplasias/patologia , Neovascularização Patológica , Neovascularização Fisiológica , Transdução de Sinais
9.
Bioelectromagnetics ; 40(6): 391-401, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31236994

RESUMO

A vascular thrombus therapy method based on magnetic-induced vibration is presented. It is a mechanicalway of removing vascular thrombus that adopts the combined use of two concepts, namely (i) magnetic-induced vibration of magnetostrictive materials and (ii) changes in physical form of thrombus under high-frequency impact and vibration. This method has many advantages that (i) eliminate the side effects of drug treatment, (ii) reduce the complexity of traditional mechanical method, and (iii) improve the reliability of treatment. Practical results obtained from the simulations and experiments are included. They verify the proposed system and indicate that this method can effectively treat vascular thrombus and reduce patient's suffering and costs. Bioelectromagnetics. 2019;40:391-401. © 2019 Bioelectromagnetics Society.


Assuntos
Vasos Sanguíneos/metabolismo , Campos Magnéticos , Trombose/terapia , Fenômenos Biomecânicos , Simulação por Computador , Humanos , Modelos Biológicos , Vibração
10.
Int J Mol Sci ; 20(12)2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31238510

RESUMO

The role of Hedgehog (Hh) signaling in vascular biology has first been highlighted in embryos by Pepicelli et al. in 1998 and Rowitch et al. in 1999. Since then, the proangiogenic role of the Hh ligands has been confirmed in adults, especially under pathologic conditions. More recently, the Hh signaling has been proposed to improve vascular integrity especially at the blood-brain barrier (BBB). However, molecular and cellular mechanisms underlying the role of the Hh signaling in vascular biology remain poorly understood and conflicting results have been reported. As a matter of fact, in several settings, it is currently not clear whether Hh ligands promote vessel integrity and quiescence or destabilize vessels to promote angiogenesis. The present review relates the current knowledge regarding the role of the Hh signaling in vasculature development, maturation and maintenance, discusses the underlying proposed mechanisms and highlights controversial data which may serve as a guideline for future research. Most importantly, fully understanding such mechanisms is critical for the development of safe and efficient therapies to target the Hh signaling in both cancer and cardiovascular/cerebrovascular diseases.


Assuntos
Vasos Sanguíneos/embriologia , Vasos Sanguíneos/metabolismo , Proteínas Hedgehog/metabolismo , Organogênese , Transdução de Sinais , Animais , Barreira Hematoencefálica/metabolismo , Diferenciação Celular , Humanos , Ligantes , Neovascularização Fisiológica
11.
Rev Cardiovasc Med ; 20(1): 19-25, 2019 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-31184092

RESUMO

Vascular aging is a major risk factor and driver of agerelated cardiovascular diseases (CVD). Atherosclerosis, hypertension, and other CVD lead to vascular dysfunction that involves multiple pathological processes such as oxidative stress, endothelial dysfunction, inflammation, and autophagy. Epigenetics refers to genetic changes that occur when the DNA remains unchanged that include DNA methylation, histone modification, and non-coding RNA. It has been reported that epigenetics plays an effective regulatory role in CVD and affects cardiovascular repair function. Presently, drugs targeting epigenetics have applications in malignant tumors and inflammation. Therefore, exploration of epigenetic mechanisms in vascular aging will allow us to understand the pathogenesis of diseases related to vascular aging. This review focuses on the pathological changes in vascular aging and analyzes the relationship between vascular aging and epigenetics. Additionally, this review focuses on the pathogenesis of vascular aging related diseases from a new perspective in order to develop epigenetic-based treatment strategies for patients with age-related cardiovascular diseases.


Assuntos
Envelhecimento/genética , Vasos Sanguíneos/metabolismo , Doenças Cardiovasculares/genética , Epigênese Genética , Fatores Etários , Envelhecimento/patologia , Animais , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/patologia , Vasos Sanguíneos/fisiopatologia , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Montagem e Desmontagem da Cromatina , Metilação de DNA , Epigênese Genética/efeitos dos fármacos , Hemodinâmica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Transdução de Sinais , Remodelação Vascular
12.
Oxid Med Cell Longev ; 2019: 5953685, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31214280

RESUMO

Type 2 diabetes (T2DM) and its complications constitute a major worldwide public health problem, with high rates of morbidity and mortality. Biomarkers for predicting the occurrence and development of the disease may therefore offer benefits in terms of early diagnosis and intervention. This review provides an overview of human studies on circulating biomarkers of oxidative stress and antioxidant defence systems and discusses their usefulness from a clinical perspective. Most case-control studies documented an increase in biomarkers of oxidative lipid, protein, and nucleic acid damage in patients with prediabetes and in those with a diagnosis of T2DM compared to controls, and similar findings were reported in T2DM with micro- and macrovascular complications compared to those without. The inconsistence of the results regarding antioxidant defence systems renders difficulty to draw a general conclusion. The clinical relevance of biomarkers of oxidative lipid and protein damage for T2DM progression is uncertain, but prospective studies suggest that markers of oxidative nucleic acid damage such as 8-hydroxy-2'-deoxyguanosine and 8-hydroxyguanosine are promising for predicting macrovascular complications of T2DM. Emerging evidence also points out the relationship between serum PON1 and serum HO1 in T2DM and its complications. Overall, enhanced oxidative damage represents an underlying mechanism of glucose toxicity in T2DM and its related micro- and macrovascular complications suggesting that it may be considered as a potential additional target for pharmacotherapy. Therefore, further studies are needed to understand whether targeting oxidative stress may yield clinical benefits. In this view, the measurement of oxidative stress biomarkers in clinical trials deserves to be considered as an additional tool to currently used parameters to facilitate a more individualized treatment of T2DM in terms of drug choice and patient selection.


Assuntos
Biomarcadores/sangue , Vasos Sanguíneos/metabolismo , Complicações do Diabetes/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , /sangue , Arildialquilfosfatase/sangue , Vasos Sanguíneos/patologia , Ensaios Clínicos como Assunto , Dano ao DNA , Heme Oxigenase-1/sangue , Humanos , Metabolismo dos Lipídeos , Estresse Oxidativo
13.
Yale J Biol Med ; 92(2): 283-290, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31249489

RESUMO

The cardiovascular (CV) system has been established to be significantly influenced by the molecular components of circadian rhythm. Oscillations of circadian rhythm occur within the circulation to affect thrombosis and blood pressure and within CV tissues including arteries, heart, and kidney to control function. Physiologic and molecular oscillations of circadian rhythm have been well connected via global, tissue-specific, and transgenic reporter mouse models of key core clock signals such as Bmal1, Period, and Clock, which can produce both pathology and protection with their mutation. With different nuances of CV clock action continuing to emerge in studies of the cardiovascular system, new questions are raised in both new and old mouse model system observations that underscore the importance, complexity, and continued study of the circadian clock mechanism in cardiovascular disease.


Assuntos
Fenômenos Fisiológicos Cardiovasculares , Relógios Circadianos/fisiologia , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/fisiologia , Ritmo Circadiano/fisiologia , Animais , Pressão Sanguínea/genética , Pressão Sanguínea/fisiologia , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/fisiologia , Relógios Circadianos/genética , Ritmo Circadiano/genética , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/genética , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/metabolismo , Regulação da Expressão Gênica , Humanos
14.
Mol Med Rep ; 20(1): 205-215, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31115522

RESUMO

Tendon adhesion is a substantial challenge for tendon repair. Thermal pretreatment (TP) may decrease inflammation by upregulating heat shock proteins (HSPs). The present study intends to identify the function that TP serves when combined with HSP70 overexpression in tendon healing and adhesion in rats. Sprague­Dawley male rats were used to establish a surgically ablative tendon postoperative suture model, and the positive expression of the HSP70 protein was measured using immunohistochemistry. Changes to the blood vessels and collagenous fiber, in addition to the maximum tensile strength and the tendon sliding distance, were detected under a microscope. Finally, HSP70, tumor growth factor ß (TGF­ß), and insulin­like growth factor 1 (IGF­1) mRNA and protein levels were all determined by employing reverse transcription­quantitative polymerase chain reaction and western blot analysis methods. The positive expression of the HSP70 protein increased following TP. Furthermore, TP reduced the infiltration of inflammatory cells and improved the collagenous arrangement, accompanied by an increased maximum tensile force and tendon gliding distance following surgery. In addition, TP increased the mRNA and protein expression levels of HSP70, TGF­ß and IGF­1. Altogether, TP increases HSP70 expression, thereby reducing postoperative traumatic inflammation and establishing tendon adhesion and promoting tendon healing. Thus, TP may be a potential strategy for the treatment of tendon adhesion.


Assuntos
Proteínas de Choque Térmico HSP70/genética , Tendões/cirurgia , Aderências Teciduais/terapia , Animais , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/patologia , Regulação da Expressão Gênica/genética , Temperatura Alta/uso terapêutico , Fator de Crescimento Insulin-Like I/genética , Masculino , RNA Mensageiro/genética , Ratos , Técnicas de Sutura , Tendões/metabolismo , Tendões/patologia , Resistência à Tração , Aderências Teciduais/genética , Aderências Teciduais/patologia , Fator de Crescimento Transformador beta/genética
15.
Cells ; 8(5)2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31052445

RESUMO

Angiogenesis, the formation of new blood vessels from pre-existing vasculature, is a physiological process that begins in utero and continues throughout life in both good health and disease. Understanding the underlying mechanism in angiogenesis could uncover a new therapeutic approach in pathological angiogenesis. Since its discovery, the Hippo signaling pathway has emerged as a key player in controlling organ size and tissue homeostasis. Recently, new studies have discovered that Hippo and two of its main effectors, Yes-associated protein (YAP) and its paralog transcription activator with PDZ binding motif (TAZ), play critical roles during angiogenesis. In this review, we summarize the mechanisms by which YAP/TAZ regulate endothelial cell shape, behavior, and function in angiogenesis. We further discuss how YAP/TAZ function as part of developmental and pathological angiogenesis. Finally, we review the role of YAP/TAZ in tumor vascular mimicry and propose directions for future work.


Assuntos
Vasos Sanguíneos/metabolismo , Neovascularização Fisiológica , Proteínas Serina-Treonina Quinases/metabolismo , Fatores de Transcrição/metabolismo , Animais , Células Endoteliais/metabolismo , Humanos , Neoplasias/irrigação sanguínea , Neoplasias/patologia
16.
Ter Arkh ; 91(4): 130-135, 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31094487

RESUMO

Obesity is closely associated with metabolic and cardiovascular diseases, including dyslipidemia, coronary artery disease, hypertension, and heart failure. Adipose tissue (AT) is identified as a complex endocrine organ, with a wide range of regulatory functions at the cellular, tissue and systemic levels. Various terms, including paracardiac, epicardial and pericardial, are used to describe the fatty deposits surrounding the heart. Among all the fat depots, perivascular AT (PVAT) is of great biological significance for the cardiovascular system due to its anatomical proximity to the vessels. Recent studies have shown the presence of a complex, bidirectional paracrine and vasocardial signaling system between the vascular wall and PVAT. In the review, we will discuss the biological role of PVAT in both the physiological state and cardiovascular pathology, emphasizing its dual proatherogenic and antiatherogenic role. Let us consider PVAT as a target for various therapeutic agents in cardiovascular diseases. We will also analyze data on the role of non-invasive techniques as a diagnostic tool for assessing coronary artery inflammation.


Assuntos
Tecido Adiposo , Vasos Sanguíneos/metabolismo , Doenças Cardiovasculares/diagnóstico , Doença da Artéria Coronariana , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Tecido Adiposo/fisiologia , Vasos Sanguíneos/fisiologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/metabolismo , Insuficiência Cardíaca , Humanos , Obesidade/patologia , Pericárdio
17.
Amyloid ; 26(3): 118-124, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31122115

RESUMO

Objectives: Previous clinical studies have shown frequent cardiac symptoms in patients with hereditary gelsolin (AGel) amyloidosis, possibly related to amyloid deposition in the heart and other internal organs. Previous studies on internal organ amyloid deposition in AGel amyloidosis have been based on small patient series. Methods: Paraffin-embedded tissue sections from 25 autopsied individuals (age at death 44.4-88.6 years) with AGel amyloidosis were stained with HE, Congo red and Herovici stains and immunohistochemistry against the low molecular weight gelsolin fraction was performed. The amount of amyloid was estimated semi-quantitatively. Results: AGel-based amyloid deposits were found in the myocardium and cardiac blood vessels in every patient. The deposits were mainly small and co-localized with regions with excess fibrosis in the myocardium. The lungs were positive for amyloid in 79%, renal parenchyma in 54% and renal blood vessels in 71% of the cases. The amount of myocardial, renal and hepatic amyloid correlated with age at death of the patients. Conclusions: We show the constant presence of AGel amyloid in the hearts of patients with AGel amyloidosis. Although the deposits were mainly small, the co-localization of amyloid with fibrosis may amplify the effect of pure amyloid deposition, possibly leading to clinical signs and symptoms.


Assuntos
Proteínas Amiloidogênicas/genética , Amiloidose/genética , Distrofias Hereditárias da Córnea/genética , Gelsolina/genética , Rim/metabolismo , Pulmão/metabolismo , Miocárdio/metabolismo , Idoso , Idoso de 80 Anos ou mais , Proteínas Amiloidogênicas/metabolismo , Amiloidose/metabolismo , Amiloidose/patologia , Autopsia , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/patologia , Distrofias Hereditárias da Córnea/metabolismo , Distrofias Hereditárias da Córnea/patologia , Feminino , Gelsolina/metabolismo , Expressão Gênica , Humanos , Imuno-Histoquímica , Rim/irrigação sanguínea , Rim/patologia , Pulmão/irrigação sanguínea , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia
18.
Int J Mol Sci ; 20(8)2019 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-31013778

RESUMO

Insulin in physiological concentrations is important to maintain vascular function. Moreover, vascular insulin resistance contributes to vascular impairment. In the elderly, other factors including hypertension, dyslipidemia, and chronic inflammation amplify senescence of vascular endothelial and smooth muscle cells. In turn, senescence increases the risk for vascular-related diseases such as arteriosclerosis, diabetes, and Alzheimer's disease. Recently, it was found that GM1 ganglioside, one of the glycolipids localized on the cell membrane, mediates vascular insulin resistance by promoting senescence and/or inflammatory stimulation. First, it was shown that increased GM1 levels associated with aging/senescence contribute to insulin resistance in human aortic endothelial cells (HAECs). Second, the expression levels of gangliosides were monitored in HAECs treated with different concentrations of tumor necrosis factor-alpha (TNFα) for different time intervals to mimic in vivo acute or chronic inflammatory conditions. Third, the levels of insulin signaling-related molecules were monitored in HAECs after TNFα treatment with or without inhibitors of ganglioside synthesis. In this review, we summarize the molecular mechanisms of insulin resistance in aged/senescent and TNFα-stimulated endothelial cells mediated by gangliosides and highlight the possible roles of gangliosides in vascular insulin resistance-related diseases.


Assuntos
Vasos Sanguíneos/metabolismo , Gangliosídeos/metabolismo , Resistência à Insulina , Insulina/metabolismo , Animais , Senescência Celular , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Humanos , Transdução de Sinais , Vasculite/etiologia , Vasculite/metabolismo
19.
Eur J Pharmacol ; 852: 167-178, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-30826323

RESUMO

2',3',5'-Tri-O-acetyl-N6-(3-hydroxyphenyl) adenosine, a cordycepin derivative that is also known as IMM-H007, is a new adenosine analogue and anti-hyperlipidaemic drug that was developed in our laboratory. It has been previously reported to alleviate atherosclerosis by regulating blood lipid levels. The purpose of the current study was to determine the protective effects of IMM-H007 on endothelial function and vascular inflammation independent of its lipid-lowering effect. Vascular reactivity was determined using a pressure myography system-120CP. Vascular inflammation was assessed to quantify leukocyte-endothelial adhesion in the mesenteric microcirculation. Relative levels of endothelial nitric oxide synthase(eNOS)activity were detected using a fluorescent nitric oxide(NO)probe, and NO production was detected using Griess reagent. Atherosclerotic plaques were evaluated with en face and cross section analyses. Here, IMM-H007 improved endothelial dysfunction through a mechanism independent of its lipid-lowering effect. IMM-H007 suppressed vascular inflammation both in the initial stage and during the progression of atherosclerosis. The in vitro study using human umbilical vein endothelial cells (HUVECs) revealed that IMM-H007 increased eNOS activity and nitric oxide production, which were closely related to the increased phosphorylation of AMP-activated protein kinase (AMPK), protein kinase B (Akt) and eNOS induced by IMM-H007. Furthermore, inhibition of AMPK by Compound C completely blocked IMM-H007-induced Akt and eNOS activation. IMM-H007 suppressed the formation of atherosclerotic lesions in ApoE-/- mice. We have presented evidence that IMM-H007 represents a potential therapeutic strategy to improve endothelial function and attenuate inflammation, and it is a promising, novel therapeutic approach to treating atherosclerosis.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adenosina/análogos & derivados , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/fisiopatologia , Dieta Hiperlipídica/efeitos adversos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Adenosina/farmacologia , Animais , Aterosclerose/prevenção & controle , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/patologia , Ativação Enzimática/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Inflamação/metabolismo , Inflamação/patologia , Inflamação/fisiopatologia , Camundongos , Camundongos Knockout para ApoE , Óxido Nítrico/biossíntese , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Necrose Tumoral alfa/farmacologia
20.
In Vitro Cell Dev Biol Anim ; 55(4): 312-322, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30887212

RESUMO

Burn is one of the common wounds in the world and using modern methods such as cell therapy can be considered as an effective strategy in the treatment of these wounds. The aim of this study is investigating the effects of using graphene quantum dots (GQDs) associated fibroblasts on treating third-degree burns in Wistar rats. In this experiment, cells were obtained by isolating fibroblasts from 13-day embryos of Wistar rats. MTT assay was performed to determine the dose of nanoparticle and cell tracker. For this study, 40 Wistar rats were burned and randomly divided into two groups of control and treatment. The treatment group was divided into three groups of daily injection of GQD nanoparticle with a concentration of 100 µg/ml, cell therapy, and cell therapy + GQDs. On days 20 and 40, skin tissue sections were prepared and stained with hematoxylin-eosin (H&E) and trichrome Masson for microscopic examination. Macroscopic and microscopic observations showed that in the treatment groups, the recovery was higher than the control. Also, cell therapy and GQD injection and simultaneous injection of cell therapy + GQDs accelerated the wound healing process and the cell therapy + GQDs were significantly more effective than nanoparticles and cell injection alone after 20 and 40 days. Histological studies indicated a significant increase in angiogenesis, number of cells, collagen synthesis, thickness of skin layers, and ultimately acceleration wound healing in treatment samples compared to controls. Based on these results, it can be concluded that simultaneous cell therapy and GQDs accelerate the repair of skin lesions in the animal models more significantly.


Assuntos
Queimaduras/terapia , Embrião de Mamíferos/citologia , Fibroblastos/transplante , Grafite/farmacologia , Pontos Quânticos/química , Cicatrização , Animais , Vasos Sanguíneos/metabolismo , Queimaduras/patologia , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Colágeno/metabolismo , Fibroblastos/efeitos dos fármacos , Nanopartículas/química , Ratos Wistar , Cicatrização/efeitos dos fármacos
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