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Akt platelet

Annette D Rieg, Said Suleiman, Carolin Anker, Eva Verjans, Rolf Rossaint, Stefan Uhlig, Christian Martin
BACKGROUND: Platelet-derived growth factor (PDGF)-BB and its receptor PDGFR are highly expressed in pulmonary hypertension (PH) and mediate proliferation. Recently, we showed that PDGF-BB contracts pulmonary veins (PVs) and that this contraction is prevented by inhibition of PDGFR-β (imatinib/SU6668). Here, we studied PDGF-BB-induced contraction and downstream-signalling in isolated perfused lungs (IPL) and precision-cut lung slices (PCLS) of guinea pigs (GPs). METHODS: In IPLs, PDGF-BB was perfused after or without pre-treatment with imatinib (perfused/nebulised), the effects on the pulmonary arterial pressure (PPA ), the left atrial pressure (PLA ) and the capillary pressure (Pcap ) were studied and the precapillary (Rpre ) and postcapillary resistance (Rpost ) were calculated...
June 19, 2018: Respiratory Research
Tzu-Yu Huang, Yi-Hsin Lin, Heng-Ai Chang, Tzu-Ying Yeh, Ya-Han Chang, Yi-Fan Chen, Ying-Chi Chen, Chun-Chun Li, Wen-Tai Chiu
Platelet-derived growth factor (PDGF) has mitogenic and chemotactic effects on fibroblasts. An increase in intracellular Ca2+ is one of the first events that occurs following the stimulation of PDGF receptors (PDGFRs). PDGF activates Ca2+ elevation by activating the phospholipase C gamma (PLCγ)-signaling pathway, resulting in ER Ca2+ release. Store-operated Ca2+ entry (SOCE) is the major form of extracellular Ca2+ influx following depletion of ER Ca2+ stores and stromal interaction molecule 1 (STIM1) is a key molecule in the regulation of SOCE...
June 18, 2018: International Journal of Molecular Sciences
Mingxia Sun, Chongdong Liu, Na Zhao, Kaikai Meng, Zhenyu Zhang
The present study investigated the predictive value of the platelet aggregation rate in postpartum deep venous thrombosis and its possible mechanism. From January 2014 to January 2016, 23 patients with postpartum deep vein thrombosis of lower extremity treated in the Department of Obstetrics of Beijing Chaoyang Hospital were as assigned as the observation group. At the same time, 25 cases with normal recovery were assigned as the control group. Blood samples were collected from all the subjects. The platelet aggregation rate was measured using a platelet aggregation apparatus...
June 2018: Experimental and Therapeutic Medicine
Muhammad Irfan, Da Hye Jeong, Hyuk-Woo Kwon, Jung-Hae Shin, Sang-Joon Park, Dongmi Kwak, Tae-Hwan Kim, Dong-Ha Lee, Hwa-Jin Park, Man Hee Rhee
BACKGROUND & PURPOSE: Ginseng (Panax ginseng C.A. Mayer) contains saponin fractions called ginsenosides, which are thought to be the main components responsible for its various pharmacological activities. Ginsenosides have cardioprotective and antiplatelet effects. In the present study, we evaluated the effects of ginsenoside Rp3 (G-Rp3) on platelet function. METHODS: The in vitro effects of G-Rp3 were evaluated on agonist-induced human and rat platelet aggregation, while [Ca2+ ]i mobilization, granule secretion, integrin αIIb β3 activation, and clot retraction were assessed in rat platelets...
June 8, 2018: Vascular Pharmacology
Hong Zhi, Fu-Han Gong, Wen-Lin Cheng, Kongbo Zhu, Long Chen, Yuyu Yao, Xingzhou Ye, Xue-Yong Zhu, Hongliang Li
BACKGROUND: Tollip, a well-established endogenous modulator of Toll-like receptor signaling, is involved in cardiovascular diseases. The aim of this study was to investigate the role of Tollip in neointima formation and its associated mechanisms. METHODS AND RESULTS: In this study, transient increases in Tollip expression were observed in platelet-derived growth factor-BB-treated vascular smooth muscle cells and following vascular injury in mice. We then applied loss-of-function and gain-of-function approaches to elucidate the effects of Tollip on neointima formation...
June 10, 2018: Journal of the American Heart Association
Sumalaxmi Janapati, Jeremy Wurtzel, Carol Dangelmaier, Bhanu Kanth Manne, Dheeraj Bhavanasi, John C Kostyak, Soochong Kim, Michael Holinstat, Satya P Kunapuli, Lawrence E Goldfinger
BACKGROUND: Many RAS family small GTPases are expressed in platelets, including RAC, RHOA, RAP, and H-/N-/RRAS1, but most of their signaling and cellular functions remain poorly understood. Like RRAS1, TC21/RRAS2 reverses HRAS-induced suppression of integrin activation in CHO cells. However, a role for TC21 in platelets has not been explored. OBJECTIVES: To determine TC21 expression in platelets, TC21 activation in response to platelet agonists, and roles of TC21 in platelet function in vitro and in vivo thrombosis...
June 8, 2018: Journal of Thrombosis and Haemostasis: JTH
Fang Wang, Thomas Bank, Gregory Malnassy, Maribel Arteaga, Na Shang, Annika Dalheim, Xianzhong Ding, Scott J Cotler, Mitchell F Denning, Michael I Nishimura, Peter Breslin, Wei Qiu
Hepatocellular carcinoma (HCC) is the fifth most common primary cancer and second largest cause of cancer-related death worldwide. The first-line oral chemotherapeutic agent sorafenib only increases survival in patients with advanced HCC by less than 3 months. Most patients with advanced HCC have shown limited response rates and survival benefits with sorafenib. Although sorafenib is an inhibitor of multiple kinases, including serine/threonine-protein kinase c-Raf, serine/threonine-protein kinase B-Raf, vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, VEGFR-3, and platelet-derived growth factor receptor β, HCC cells are able to escape from sorafenib treatment using other pathways that the drug insufficiently inhibits...
June 2018: Hepatology Communications
Yuan-Hsi Wang, Yuh-Ching Twu, Chung-Kwe Wang, Fu-Zhen Lin, Chun-Ya Lee, Yi-Jen Liao
Liver fibrosis is the first step toward the progression to cirrhosis, portal hypertension, and hepatocellular carcinoma. A high-cholesterol diet is associated with liver fibrosis via the accumulation of free cholesterol in hepatic stellate cells (HSCs). Niemann-Pick type C2 (NPC2) plays an important role in the regulation of intracellular free cholesterol homeostasis via direct binding with free cholesterol. Previously, we reported that NPC2 was downregulated in liver cirrhosis tissues. Loss of NPC2 enhanced the accumulation of free cholesterol in HSCs and made them more susceptible to transforming growth factor (TGF)-β1...
June 5, 2018: International Journal of Molecular Sciences
Maram Morjen, Houcemeddine Othman, Zaineb Abdelkafi-Koubaa, Erij Messadi, Jed Jebali, Mohamed El Ayeb, Najet Srairi Abid, José Luis, Naziha Marrakchi
Through the recent development of knowledge in biotechnology and bioinformatics, snake venoms are widely used to develop new drugs to treat diseases such as hypertension and cancer. We have previously reported that Lebetin 2 isolated from Macrovipera lebetina transmediterranea venom displays a potent anti-platelet activity and exerts a cardioprotective effect in ischemia-reperfusion (IR) injury model. Here, we report that Lebetin 2 possess an anti-tumor effect by targeting the integrin receptor function. It was thus able to inhibit both adhesion and migration of pheochromocytoma cells (PC12) and α1β1 integrin-expressing CHO cells (CHO-α1) to type I and IV collagens...
June 2, 2018: International Journal of Biological Macromolecules
Muhammad Irfan, Dahye Jeong, Evelyn Saba, Hyuk-Woo Kwon, Jung-Hae Shin, Bo-Ra Jeon, Suk Kim, Sung-Dae Kim, Dong-Ha Lee, Seung-Yeol Nah, Man Hee Rhee
Panax ginseng (P. ginseng), one of the most valuable medicinal plants, is known for its healing and immunobooster properties and has been widely used in folk medicine against cardiovascular diseases, including stroke and heart attack. In this study, we explored the anti-platelet activity of gintonin (a recently discovered non-saponin fraction of ginseng) against agonist-induced platelet activation. In vitro effects of gintonin on agonist-induced human and rat platelet aggregation, granule secretion, integrin αIIb β3 activation, and intracellular calcium ion ([Ca2+ ]i ) mobilization were examined...
June 5, 2018: Platelets
Typhaine Anquetil, Bernard Payrastre, Marie-Pierre Gratacap, Julien Viaud
Our knowledge on the role of the different lipid messengers produced by phosphoinositide 3-kinases (PI3Ks) in normal and cancer cells as well as in platelets during arterial thrombosis has greatly expanded these last 15 years. PI3Ks are a family of lipid kinases that catalyze the phosphorylation of the D3 position of the inositol ring of phosphoinositides to produce phosphatidylinositol 3-phosphate (PtdIns3P), phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2 ), and phosphatidylinositol-3,4,5 trisphosphate (PtdIns(3,4,5)P3 )...
June 4, 2018: Cancer Metastasis Reviews
Jing Li, Liang Hui, Qianyan Kang, Rong Li
Aberrant proliferation and migration of retinal pigment epithelium (RPE) cells contributes to the pathology of various ocular diseases. miR-27b has been reported to be crucial in the regulation of cell differentiation, proliferation, apoptosis, and migration. However, the role of miR-27b on RPE proliferation and migration remains largely unknown. Here the effect of miR-27b on ARPE-19 cells under platelet-derived growth factor (PDGF)-BB stimulation was explored. In this study, we found that the expression level of miR-27b was significantly reduced in ARPE-19 cells under PDGF-BB stimulation...
May 24, 2018: Pathology, Research and Practice
Run-Hao Jiang, Xiao-Quan Xu, Chen-Jiang Wu, Shan-Shan Lu, Qing-Quan Zu, Lin-Bo Zhao, Sheng Liu, Hai-Bin Shi
OBJECTIVE: The role of CD40/CD40 ligand (CD40L) in microvascular thrombosis is now widely accepted. However, the exact mechanisms linking the CD40/CD40L system and the soluble form of CD40L (sCD40L) with microvascular thrombosis are currently a topic of intensive research. The objective of this study was to assess the potential mechanisms in CD40/CD40L system-regulated microvascular thrombosis after focal ischemia/reperfusion (I/R). METHODS: Rats were subjected to 60-min transient middle cerebral artery occlusion (MCAO)...
May 29, 2018: Neurological Research
Doreswamy Kenchegowda, Betre Legesse, Bernadette Hritzo, Cara Olsen, Saeed Aghdam, Amandeep Kaur, William Culp, Alexandrine Derrien-Colemyn, Grant Severson, Maria Moroni
Although bone marrow aplasia has been considered for the past decades as the major contributor of radiation-induced blood disorders, cytopenias alone are insufficient to explain differences in the prevalence of bleeding. In this study, the minipig was used as a novel preclinical model of hematopoietic acute radiation syndrome to assess if factors other than platelet counts correlated with bleeding and survival. We sought to determine whether radiation affected the insulin-like growth factor-1 (IGF-1) pathway, a growth hormone with cardiovascular and radioprotective features...
May 29, 2018: Radiation Research
Daniel da Motta Girardi, Tatiana Strava Correa, Marcela Crosara Teixeira, Gustavo Dos Santos Fernandes
BACKGROUND: Hepatocellular carcinoma is the fifth most common cancer globally and the second leading cause of cancer-related mortality worldwide. Despite the established efficacy of screening programs for at-risk individuals, most patients are diagnosed at later stages of disease, wherein the tumor characteristics or liver disease progressions do not allow for curative interventions. Many cytotoxic chemotherapeutic agents have been tested in patients with advanced disease with disappointing outcomes and poor tolerance; therefore, no standard systemic therapy emerged until the approval of sorafenib in 2006...
May 28, 2018: Journal of Gastrointestinal Cancer
Shilei Chen, Mengjia Hu, Mingqiang Shen, Song Wang, Cheng Wang, Fang Chen, Yong Tang, Xinmiao Wang, Hao Zeng, Mo Chen, Jining Gao, Fengchao Wang, Yongping Su, Yang Xu, Junping Wang
It is known that insulin-like growth factor-1 (IGF-1) also functions as a hematopoietic factor, while its direct effect on thrombopoiesis remains unclear. In this study, we show that IGF-1 is able to promote CD34+ cell differentiation toward megakaryocytes (MKs), as well as the facilitation of proplatelet formation (PPF) and platelet production from cultured MKs. The in vivo study demonstrates that IGF-1 administration accelerates platelet recovery in mice after 6.0Gy of irradiation and in mice that received bone marrow transplantation (BMT) following 10...
May 25, 2018: Blood
Wei Song, Yuan-Yuan Ma, Shuo Miao, Ru-Ping Yang, Ying Zhu, Dan Shu, Meng Lu, Rong Ma, Zhang-Yin Ming
Salvia miltiorrhiza Bunge contains various active constituents, some of which have been developed as commercially available medicine. Moreover, some other ingredients in Salvia miltiorrhiza play roles in anti-platelet activity. The aim of the present study was to investigate the effects and the underlying mechanism of miltirone, a lipophilic compound of Salvia miltiorrhiza Bunge. The ability of miltirone to modulate platelet function was investigated by a variety of in vitro and in vivo experiments. Platelet aggregation and dense granule secretion induced by various agonists were measured with platelet aggregometer...
May 23, 2018: Acta Pharmacologica Sinica
T A Blair, S F Moore, T G Walsh, J L Hutchinson, T N Durrant, K E Anderson, A W Poole, I Hers
Phosphoinositide 3-kinase (PI3K) plays an important role in platelet function and contributes to platelet hyperreactivity induced by elevated levels of circulating peptide hormones, including thrombopoietin (TPO). Previous work established an important role for the PI3K isoform; p110β in platelet function, however the role of p110α is still largely unexplored. Here we sought to investigate the role of p110α in TPO-mediated hyperactivity by using a conditional p110α knockout (KO) murine model in conjunction with platelet functional assays...
May 21, 2018: Cellular Signalling
Yong Lan, Yongjun Li, Dajun Li, Peng Li, Jiyang Wang, Yongpeng Diao, Guodong Ye, Yangfang Li
Endothelial cells are critical in angiogenesis and maintain the homeostasis of the blood‑brain barrier (BBB). Platelets (PLTs) are essential in vascular biology, including angiogenesis. The present study aimed to investigate the effect of PLTs on the aging of endothelial cells. Human brain microvascular endothelial cells (HBMECs) and human astrocytes were co‑cultured to mimic the BBB. Transmission electron microscopy was used to observe the engulfment of PLTs. Confocal microscopy was used to observe the co‑localization of PLTs, girders of actin filament (girdin) and phosphorylated (p‑)girdin...
May 17, 2018: International Journal of Molecular Medicine
Qi Ma, Chongzhuo Zhu, Weilin Zhang, Na Ta, Rong Zhang, Lei Liu, Du Feng, Heping Cheng, Junling Liu, Quan Chen
Platelets undergo apoptosis in response to a variety of stimuli in the circulation. Mitochondria in platelets are essential for their apoptosis. Specifically, pro-survival protein BCL-xL on mitochondria is the key regulator of platelet lifespan. Here we identify an outer mitochondrial membrane protein FUNDC2 for platelet survival. FUNDC2 knockout mice carrying excessively apoptotic platelets exhibit thrombocytopenia in response to hypoxia. Mechanistically, FUNDC2 binds the lipid PIP3 via its unique, highly conserved N-terminal motif...
May 21, 2018: Cell Death and Differentiation
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