Role of Platelet-Activating Factor in Cardiovascular Pathophysiology

2000 ◽  
Vol 80 (4) ◽  
pp. 1669-1699 ◽  
Author(s):  
Giuseppe Montrucchio ◽  
Giuseppe Alloatti ◽  
Giovanni Camussi
Keyword(s):  
Cardiovascular System ◽  
Cell Biology ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Experimental Studies ◽  
Platelet Activating Factor ◽  
Biologically Active ◽  
Endothelial Cell Migration

Platelet-activating factor (PAF) is a phospholipid mediator that belongs to a family of biologically active, structurally related alkyl phosphoglycerides. PAF acts via a specific receptor that is coupled with a G protein, which activates a phosphatidylinositol-specific phospholipase C. In this review we focus on the aspects that are more relevant for the cell biology of the cardiovascular system. The in vitro studies provided evidence for a role of PAF both as intercellular and intracellular messenger involved in cell-to-cell communication. In the cardiovascular system, PAF may have a role in embryogenesis because it stimulates endothelial cell migration and angiogenesis and may affect cardiac function because it exhibits mechanical and electrophysiological actions on cardiomyocytes. Moreover, PAF may contribute to modulation of blood pressure mainly by affecting the renal vascular circulation. In pathological conditions, PAF has been involved in the hypotension and cardiac dysfunctions occurring in various cardiovascular stress situations such as cardiac anaphylaxis and hemorrhagic, traumatic, and septic shock syndromes. In addition, experimental studies indicate that PAF has a critical role in the development of myocardial ischemia-reperfusion injury. Indeed, PAF cooperates in the recruitment of leukocytes in inflamed tissue by promoting adhesion to the endothelium and extravascular transmigration of leukocytes. The finding that human heart can produce PAF, expresses PAF receptor, and is sensitive to the negative inotropic action of PAF suggests that this mediator may have a role also in human cardiovascular pathophysiology.

scholarly journals MiR-125 Family in Cardiovascular and Cerebrovascular Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Yang Wang ◽  
Jing Tan ◽  
Lu Wang ◽  
Gaiqin Pei ◽  
Hongxin Cheng ◽  
...  
Keyword(s):  
Cardiovascular System ◽  
Ischemia Reperfusion Injury ◽  
Mirna Family ◽  
Ischemia Reperfusion ◽  
Cerebrovascular Diseases ◽  
Clinical Applications ◽  
Abnormal Development ◽  
Prevention And Treatment ◽  
Huge Challenge

Cardiovascular and cerebrovascular diseases are a serious threaten to the health of modern people. Understanding the mechanism of occurrence and development of cardiovascular and cerebrovascular diseases, as well as reasonable prevention and treatment of them, is a huge challenge that we are currently facing. The miR-125 family consists of hsa-miR-125a, hsa-miR-125b-1 and hsa-miR-125b-2. It is a kind of miRNA family that is highly conserved among different species. A large amount of literature shows that the lack of miR-125 can cause abnormal development of the cardiovascular system in the embryonic period. At the same time, the miR-125 family participates in the occurrence and development of a variety of cardiovascular and cerebrovascular diseases, including myocardial ischemia, atherosclerosis, ischemia-reperfusion injury, ischemic stroke, and heart failure directly or indirectly. In this article, we summarized the role of the miR-125 family in the development and maturation of cardiovascular system, the occurrence and development of cardiovascular and cerebrovascular diseases, and its important value in the current fiery stem cell therapy. In addition, we presented this in the form of table and diagrams. We also discussed the difficulties and challenges faced by the miR-125 family in clinical applications.

Critical role of reactive nitrogen species in lung ischemia–reperfusion injury

2003 ◽  
Vol 22 (7) ◽  
pp. 784-793 ◽  
Author(s):  
Babu V Naidu ◽  
Charles Fraga ◽  
Andrew L Salzman ◽  
Csaba Szabo ◽  
Edward D Verrier ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Reactive Nitrogen Species ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Reactive Nitrogen ◽  
Nitrogen Species

scholarly journals Critical role of acidic sphingomyelinase in murine hepatic ischemia-reperfusion injury

Hepatology ◽  
2006 ◽  
Vol 44 (3) ◽  
pp. 561-572 ◽  
Author(s):  
Laura Llacuna ◽  
Montserrat Marí ◽  
Carmen Garcia-Ruiz ◽  
José C. Fernandez-Checa ◽  
Albert Morales
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Hepatic Ischemia ◽  
Hepatic Ischemia Reperfusion

Abstract 15175: Critical Role of Sodium-Glucose Cotransporter 1 in the Cardioprotection Through the Maintenance of Energy Production During Ischemia-Reperfusion Injury

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Yusuke Kashiwagi ◽  
Tomohisa Nagoshi ◽  
Takuya Yoshino ◽  
Ryuko Anzawa ◽  
Michihiro Yoshimura
Keyword(s):  
Reperfusion Injury ◽  
Energy Production ◽  
Glucose Utilization ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Glucose Transporters ◽  
Sodium Glucose Cotransporter ◽  
Atp Generation

Glucose becomes an important preferential substrate for cardiac metabolism and ATP generation under specific pathological conditions, such as ischemia. Glucose utilization is initiated by glucose uptake, which is mainly controlled by glucose transporters. Although the role of passive glucose transporters (GLUTs) has been investigated intensively, little is known about the functional significance of the other active transporter, sodium-glucose cotransporter 1 (SGLT1), in the heart. We herein hypothesized that cardiac SGLT1 plays a critical role for cardioprotection during ischemia-reperfusion injury (IRI), possibly through the enhanced glucose utilization for the energy production. To test this, we studied the effects of 10-4 M of phlorizin, SGLT1 inhibitor, on the baseline function and its response to global ischemia (20 minutes)-reperfusion (40 minutes) injury in mouse Langendorff perfusion model, where SGLT1, but not SGLT2, is highly expressed, as confirmed by immunoblotting assay. Although phlorizin did not affect baseline function, its administration during IRI significantly impaired recovery in left ventricular contraction (% recovery of baseline; 67.3±4.5 vs. 89.7±6.8%, n=5 each, P<0.05) and rate pressure product (18600±1290 vs. 25100±1010 mmHg•bpm, n=5 each, P<0.01), associated with increased infarct size demonstrated by TTC staining as well as CPK activity released into the perfusate (20.8±9.5 vs. 2.0±0.6 U•g, n≥3, P<0.05). Of note, the onset of ischemic contracture, which is thought to be initiated by ATP depletion in cardiomyocytes, was earlier with phlorizin perfusion (288±21 vs. 364±27 sec, n≥8, P<0.05). Consistent with this, the significant reduction of tissue ATP content was observed in phlorizin perfused heart (4.81±0.61 vs. 6.87±0.13 μmol/g tissue, n≥4, P<0.05). In conclusion, these data demonstrate that SGLT1 represents an important cardioprotective mechanism against IRI possibly through the maintenance of ATP generation. Our findings shed new light on the essential role of SGLT1 for the optimization of cardiac energy metabolism by the enhanced glucose availability during ischemia, thus leading to substantial myocardial protection after severe ischemic insults.

138 CRITICAL ROLE OF CHOLESTEROL IN THE SENSITIZATION OF STEATOTIC LIVER TO ISCHEMIA/REPERFUSION INJURY

2009 ◽  
Vol 50 ◽  
pp. S56
Author(s):  
L. Llacuna ◽  
A. Morales ◽  
A. Fernandez ◽  
J.C. Fernandez-Checa ◽  
C. Garcia-Ruiz
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Steatotic Liver

scholarly journals Emerging role of VCP/p97 in cardiovascular diseases: novel insights and therapeutic opportunities

2021 ◽  
Author(s):  
Hongyang Shu ◽  
Yizhong Peng ◽  
Weijian Hang ◽  
Ning Zhou ◽  
Dao Wen Wang
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Reperfusion Injury ◽  
Cardiovascular System ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Potential ◽  
Ischemia Reperfusion ◽  
Heart Research

Valosin-containing protein (VCP/p97) is a member of the conserved type II AAA+ (ATPases associated with diverse cellular activities) family of proteins with multiple biological functions, especially in protein homeostasis. Mutations in VCP/p97 are reportedly related to unique autosomal dominant diseases, which may worsen cardiac function. Although the structure of VCP/p97 has been clearly characterized, with reports of high abundance in the heart, research focusing on the molecular mechanisms underpinning the roles of VCP/p97 in the cardiovascular system has been recently undertaken over the past decades. Recent studies have shown that VCP/p97 deficiency affects myocardial fibers and induces heart failure, while overexpression of VCP/p97 eliminates ischemia/reperfusion injury and relieves pathological cardiac hypertrophy caused by cardiac pressure overload, which is related to changes in the mitochondria and calcium overload. However, certain studies have drawn opposing conclusions, including the mitigation of ischemia/reperfusion injury via inhibition of VCP/p97 ATPase activity. Nevertheless, these emerging studies shed light on the role of VCP/p97 and its therapeutic potential in cardiovascular diseases. In other words, VCP/p97 may be involved in the development of cardiovascular disease, and is anticipated to be a new therapeutic target. This review summarizes current findings regarding VCP/p97 in the cardiovascular system for the first time, and discusses the role of VCP/p97 in cardiovascular disease.

Abstract 98: Reducing Mitochondrial, But Not Cytosolic Iron, Protects The Heart Against Ischemia-reperfusion Injury

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Hsiang-Chun J Chang ◽  
Rongxue Wu ◽  
Hossein Ardehali
Keyword(s):  
Cardiac Function ◽  
Iron Homeostasis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Cellular Damage ◽  
Antioxidant Systems ◽  
Mitochondrial Iron

Introduction: Iron is essential for the activity of a large number of cellular proteins, but excess free iron can cause cellular damage through production of reactive oxygen species (ROS). Mitochondria are the major site of cellular iron homeostasis, and we recently showed the mitochondrial iron export is mediated by ATP-binding cassette protein-B8 (ABCB8). The role of mitochondrial iron in ischemia-reperfusion (I/R) injury in the heart has not been examined. We hypothesize that mitochondrial iron has a critical role in I/R damage and a reduction of mitochondrial iron is protective against I/R injury through a reduction in ROS. Results: Cardiomyocyte-specific ABCB8 transgenic (TG) mice had significantly lower mitochondrial iron in the heart than nontransgenic (NTG) littermates at baseline, but their cardiac function and the expression of key antioxidant systems were indistinguishable from NTG littermates. To study the role of mitochondrial iron in I/R injury, we subjected ABCB8 TG mice to I/R. TG mice displayed significantly less apoptosis compared to NTG littermates (11.76% vs. 17.63%, p<0.05, n=4-6) and had significantly reduced lipid peroxidation products 48 hours after I/R. To further confirm that our in vivo finding was due to reduced mitochondrial iron, we studied the effect of pharmacological reduction of mitochondrial iron in vitro. 2,2-bipyridyl (BPD) is a mitochondria-accessible iron chelator while deferoxamine (DFO) has poor penetrance into mitochondria. Treating rat cardiomyoblasts H9C2 with BPD but not DFO significantly reduced chelatable mitochondrial iron, as measured by staining cells with rhodamine B-[(1,10-phenanthrolin-5-yl)aminocarbonyl]benzyl ester. In addition, BPD but not DFO pretreatment protected cells against H2O2 induced cell death (p<0.05). BPD treatment in mice decreased baseline mitochondrial iron and significantly preserved cardiac function after I/R. Conclusions: Our findings demonstrate that selective reduction in mitochondrial iron is protective in I/R injury, and show that mitochondrial iron is a source of ROS and cellular damage in I/R. Thus, targeting mitochondrial iron with selective iron chelators, as studied in our system, may provide a novel approach for treatment of ischemic heart disease.

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