scholarly journals The development of the blood clotting initiation conceptions: from A.A. Schmidt to D.M Zubairov

2013 ◽  
Vol 94 (5) ◽  
pp. 755-760 ◽  
Author(s):  
V N Timerbaev ◽  
S V Kiselev
Keyword(s):  
Blood Coagulation ◽  
Molecular Mechanisms ◽  
Vascular Wall ◽  
Cellular Membranes ◽  
Initiation Mechanism ◽  
Modern Biology ◽  
Signal Systems ◽  
Contact Complex ◽  
Thromboplastic Activity ◽  
Tissue Thromboplastin

The objective of the review is to cover the formation of modern understanding of molecular mechanisms of blood coagulation initiation. It was provided mainly by the research of Professor D.M. Zubairov and his colleagues. Since 1963, he has established that blood coagulation initiation is not connected to the phenomenon of vascular wall moistening and contact complex factors activation. Research of the thromboplastic activity distribution in tissue cells, blood and in the serum phospholipid microparticles allowed to conclude that blood coagulation is initiated by long-term expression of tissue factor and rapid massive alterations in cellular membranes. This was confirmed by the detection of the turned phospholipids mesophases in tissue thromboplastin preparations and heterogeneity of vitamin К-depending factors binding. Based on the results of the research, a functional conception of blood coagulation initiation by phase alteration of bilayer structure of cellular membranes to a mesomorphic structure was developed. It is caused by different agonists through receptor dependant Са 2+-mobilizing cell signal systems or by massive migration of calcium ions into the cell at its damage. An initial bioimitating non-enzymatic proteolysis vitamin of К-dependant factors and their massive enzymatic activating in the ensembles of enzymatic complexes takes place on heterophase phospholipids surface. Clotting is limited by blood and tissue macrophages, removing cells and phospholipids particles with heterophase surface from cell circulation, and also by anticoagulant factors action. Based on this conception, the researches revealed the pathogenetic of role thrombogenic micro vesicles originating form the cellular membranes transformation in the development of disseminated intravascular coagulation syndrome, myocardial infarction, leucosis, autoimmune and infectious diseases. Finding out the basic concepts of blood coagulation initiation mechanism puts D.M. Zubairov in one row with scientists, pawning the bases of modern biology and medicine.

Postischemic Revascularization: From Cellular and Molecular Mechanisms to Clinical Applications

2013 ◽  
Vol 93 (4) ◽  
pp. 1743-1802 ◽  
Author(s):  
Jean-Sébastien Silvestre ◽  
David M. Smadja ◽  
Bernard I. Lévy
Keyword(s):  
Progenitor Cells ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Therapeutic Option ◽  
Vascular Wall ◽  
Arterial Disease ◽  
Cellular Mechanisms ◽  
Collateral Growth ◽  
Vessel Growth ◽  
Ischemic Diseases

After the onset of ischemia, cardiac or skeletal muscle undergoes a continuum of molecular, cellular, and extracellular responses that determine the function and the remodeling of the ischemic tissue. Hypoxia-related pathways, immunoinflammatory balance, circulating or local vascular progenitor cells, as well as changes in hemodynamical forces within vascular wall trigger all the processes regulating vascular homeostasis, including vasculogenesis, angiogenesis, arteriogenesis, and collateral growth, which act in concert to establish a functional vascular network in ischemic zones. In patients with ischemic diseases, most of the cellular (mainly those involving bone marrow-derived cells and local stem/progenitor cells) and molecular mechanisms involved in the activation of vessel growth and vascular remodeling are markedly impaired by the deleterious microenvironment characterized by fibrosis, inflammation, hypoperfusion, and inhibition of endogenous angiogenic and regenerative programs. Furthermore, cardiovascular risk factors, including diabetes, hypercholesterolemia, hypertension, diabetes, and aging, constitute a deleterious macroenvironment that participates to the abrogation of postischemic revascularization and tissue regeneration observed in these patient populations. Thus stimulation of vessel growth and/or remodeling has emerged as a new therapeutic option in patients with ischemic diseases. Many strategies of therapeutic revascularization, based on the administration of growth factors or stem/progenitor cells from diverse sources, have been proposed and are currently tested in patients with peripheral arterial disease or cardiac diseases. This review provides an overview from our current knowledge regarding molecular and cellular mechanisms involved in postischemic revascularization, as well as advances in the clinical application of such strategies of therapeutic revascularization.

scholarly journals Identification of Aortic Proteins Involved in Arterial Stiffness in Spontaneously Hypertensive Rats Treated With Perindopril:A Proteomic Approach

2021 ◽  
Vol 12 ◽  
Author(s):  
Danyelle S. Miotto ◽  
Aline Dionizio ◽  
André M. Jacomini ◽  
Anderson S. Zago ◽  
Marília Afonso Rabelo Buzalaf ◽  
...  
Keyword(s):  
Arterial Stiffness ◽  
Spontaneously Hypertensive Rats ◽  
Wistar Rats ◽  
Molecular Mechanisms ◽  
Rho Kinase ◽  
Vascular Wall ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Cytoskeleton Organization ◽  
Proteomic Approach

Arterial stiffness, frequently associated with hypertension, is associated with disorganization of the vascular wall and has been recognized as an independent predictor of all-cause mortality. The identification of the molecular mechanisms involved in aortic stiffness would be an emerging target for hypertension therapeutic intervention. This study evaluated the effects of perindopril on pulse wave velocity (PWV) and on the differentially expressed proteins in aorta of spontaneously hypertensive rats (SHR), using a proteomic approach. SHR and Wistar rats were treated with perindopril (SHRP) or water (SHRc and Wistar rats) for 8 weeks. At the end, SHRC presented higher systolic blood pressure (SBP, +70%) and PWV (+31%) compared with Wistar rats. SHRP had higher values of nitrite concentration and lower PWV compared with SHRC. From 21 upregulated proteins in the aortic wall from SHRC, most of them were involved with the actin cytoskeleton organization, like Tropomyosin and Cofilin-1. After perindopril treatment, there was an upregulation of the GDP dissociation inhibitors (GDIs), which normally inhibits the RhoA/Rho-kinase/cofilin-1 pathway and may contribute to decreased arterial stiffening. In conclusion, the results of the present study revealed that treatment with perindopril reduced SBP and PWV in SHR. In addition, the proteomic analysis in aorta suggested, for the first time, that the RhoA/Rho-kinase/Cofilin-1 pathway may be inhibited by perindopril-induced upregulation of GDIs or increases in NO bioavailability in SHR. Therefore, we may propose that activation of GDIs or inhibition of RhoA/Rho-kinase pathway could be a possible strategy to treat arterial stiffness.

CALCIUM AND VITAMIN : EFFECTS ON BONE TISSUE AND VASCULAR REMODELING (LITERATURE REVIEW)

2021 ◽  
pp. 1200-1208
Author(s):  
С. В. Булгакова ◽  
Е. В. Тренева ◽  
Н. О. Захарова ◽  
А. В. Николаева
Keyword(s):  
Literature Review ◽  
Vascular Remodeling ◽  
Molecular Mechanisms ◽  
Vascular Wall ◽  
Arterial Calcification ◽  
Mineral Density ◽  
Treatment And Prevention ◽  
Calcium Deposits ◽  
Local Accumulation ◽  
Progression Of Atherosclerosis

Препараты кальция входят в схемы лечения и профилактики низкой минеральной плотности костной ткани. Однако последние научные исследования показали, что дополнительное поступление кальция может увеличить риск сердечно-сосудистых заболеваний. Это связано с отложением кальция в эндотелии кровеносных сосудов. Значимость минерализации сосудистой стенки не ограничивается локальным накоплением кальциевых депозитов, но в значительной мере определяется их активирующим влиянием на прогрессирование атеросклероза. Витамин К играет важную роль в гомеостазе кальция, снижает артериальную кальцификацию и артериальную жесткость и, как следствие, оказывает протективный эффект при приеме кальция. В данном обзоре литературы представлена современная информация о кальциевом парадоксе, обсуждаются основные молекулярные механизмы кальцификации сосудов, рассмотрены терапевтические стратегии лечения витамином К . Calcium preparations are included in the treatment and prevention regimens for low bone mineral density. However, recent scientific studies have shown that additional calcium intake can increase the risk of heart disease, which is associated with the deposition of calcium in the endothelium of blood vessels. The significance of vascular wall mineralization is not limited to local accumulation of calcium deposits, but is largely determined by their activating effect on the progression of atherosclerosis. Vitamin K plays an important role in calcium homeostasis, reduces arterial calcification and arterial stiffness and, as a result, has a protective effect when taking calcium. This literature review provides current information about the calcium paradox, discusses the main molecular mechanisms of vascular calcification, and considers therapeutic strategies for vitamin К treatment.

scholarly journals Anticoagulant proteins from snake venoms: structure, function and mechanism

2006 ◽  
Vol 397 (3) ◽  
pp. 377-387 ◽  
Author(s):  
R. Manjunatha Kini
Keyword(s):  
Structure Function ◽  
Blood Coagulation ◽  
Snake Venom ◽  
Molecular Mechanisms ◽  
Cerebrovascular Diseases ◽  
Clot Formation ◽  
Snake Venoms ◽  
New Anticoagulants ◽  
Physiological Processes ◽  
Made In

Over the last several decades, research on snake venom toxins has provided not only new tools to decipher molecular details of various physiological processes, but also inspiration to design and develop a number of therapeutic agents. Blood circulation, particularly thrombosis and haemostasis, is one of the major targets of several snake venom proteins. Among them, anticoagulant proteins have contributed to our understanding of molecular mechanisms of blood coagulation and have provided potential new leads for the development of drugs to treat or to prevent unwanted clot formation. Some of these anticoagulants exhibit various enzymatic activities whereas others do not. They interfere in normal blood coagulation by different mechanisms. Although significant progress has been made in understanding the structure–function relationships and the mechanisms of some of these anticoagulants, there are still a number of questions to be answered as more new anticoagulants are being discovered. Such studies contribute to our fight against unwanted clot formation, which leads to death and debilitation in cardiac arrest and stroke in patients with cardiovascular and cerebrovascular diseases, arteriosclerosis and hypertension. This review describes the details of the structure, mechanism and structure–function relationships of anticoagulant proteins from snake venoms.

Potential function of cholesterol in blood coagulation: Amplification of phospholipid thromboplastic activity

Lipids ◽  
1971 ◽  
Vol 6 (2) ◽  
pp. 139-141 ◽  
Author(s):  
Oyvind Sorbye ◽  
Fred C. Phillips ◽  
W. O. Lundberg
Keyword(s):  
Blood Coagulation ◽  
Potential Function ◽  
Thromboplastic Activity

The Circulating Anticoagulant in Disseminated Lupus Erythematosus

1961 ◽  
Vol 05 (02) ◽  
pp. 250-255 ◽  
Author(s):  
Herbert A. Perkins ◽  
D. J Acra
Keyword(s):  
Blood Coagulation ◽  
Lupus Erythematosus ◽  
Coagulation Factor ◽  
Tissue Thromboplastin ◽  
Low Levels

SummaryThe circulating anticoagulant in a case of lupus erythematosus was demonstrated to accelerate the disappearance of formed thromboplastin. We were unable to show that it acted against any single blood coagulation factor. We suggest that its action may be entirely explained on the basis of destruction of the final prothrombin converting factor, with and without the presence of tissue thromboplastin. This hypothesis still leaves no explanation for the consistently low levels of prothrombin in this condition.

Crosstalk between Platelet and Bacteria: A Therapeutic Prospect

2019 ◽  
Vol 25 (38) ◽  
pp. 4041-4052
Author(s):  
Vivek K. Yadav ◽  
Pradeep K. Singh ◽  
Vishnu Agarwal ◽  
Sunil K. Singh
Keyword(s):  
Platelet Activation ◽  
Molecular Mechanisms ◽  
Thrombus Formation ◽  
Critical Role ◽  
Direct Interaction ◽  
Vascular Wall ◽  
Cardiovascular Complications ◽  
Bacterial Cells ◽  
Platelet Surface ◽  
Wide Range

Platelets are typically recognized for their roles in the maintenance of hemostasis and vascular wall repair to reduce blood loss. Beyond hemostasis, platelets also play a critical role in pathophysiological conditions like atherosclerosis, stroke, thrombosis, and infections. During infection, platelets interact directly and indirectly with bacteria through a wide range of cellular and molecular mechanisms. Platelet surface receptors such as GPIbα, FcγRIIA, GPIIbIIIa, and TLRs, etc. facilitate direct interaction with bacterial cells. Besides, the indirect interaction between platelet and bacteria involves host plasma proteins such as von Willebrand Factor (vWF), fibronectin, IgG, and fibrinogen. Bacterial cells induce platelet activation, aggregation, and thrombus formation in the microvasculature. The activated platelets induce the Neutrophil Extracellular Traps (NETs) formation, which further contribute to thrombosis. Thus, platelets are extensively anticipated as vital immune modulator cells during infection, which may further lead to cardiovascular complications. In this review, we cover the interaction mechanisms between platelets and bacteria that may lead to the development of thrombotic disorders. Platelet receptors and other host molecules involved in such interactions can be used to develop new therapeutic strategies to combat against infection-induced cardiovascular complications. In addition, we highlight other receptor and enzyme targets that may further reduce infection-induced platelet activation and various pathological conditions.

I All-Union conference "vascular wall damage and hemostasis"

1982 ◽  
Vol 63 (1) ◽  
pp. 72-73
Keyword(s):  
Blood Coagulation ◽  
Vascular Wall ◽  
Vascular Pathology ◽  
Blood Coagulation Disorders ◽  
Coagulation Disorders ◽  
Close Attention ◽  
Practical Medicine ◽  
Union Conference ◽  
Therapeutic Possibilities

(Poltava. 21-22 / XII 1981) Pathology of the vascular wall and blood coagulation disorders have long attracted close attention of specialists in various fields of theoretical and practical medicine. Therefore, the conference devoted to the study of the influence of vascular pathology on the processes of blood coagulation, the diagnosis of these disorders, as well as the consideration of the therapeutic possibilities of their correction, aroused great interest. The leading experts of our country took part in it.

Abstract 187: Paraoxonase-2 Regulates Blood Coagulation through Endothelial Redox-Signaling and Inflammation

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Julia Ebert ◽  
Petra Wilgenbus ◽  
Sven Horke
Keyword(s):  
Oxidative Stress ◽  
Bone Marrow ◽  
Blood Coagulation ◽  
Coagulation Factors ◽  
Vascular Wall ◽  
Inflammatory Processes ◽  
Gene Expression Studies ◽  
Underlying Mechanisms ◽  
Membrane Exposure ◽  
Bone Marrow Chimeras

Background: Enhanced coagulation increases the risk for cardiovascular diseases (CVDs) such as stroke, myocardial infarction or atherosclerosis. Increased oxidative stress and inflammation, predominantly in the vascular wall and platelets, are important underlying mechanisms of a pro-coagulant state. Paraoxonase-2 (PON2), an anti-oxidative protein with anti-inflammatory properties, has an emergent role in CVDs, as it counter-acts atherosclerosis. Previous studies revealed enhanced atherosclerosis in PON2-/- mice and diminished PON2 expression in human atherosclerotic endothelium. We hypothesized that PON2 affects coagulation by controlling redox-mediated inflammatory processes provoking atherosclerosis. Methods and Results: In several coagulation tests, PON2-/- mice showed significantly shortened clotting times (8.58±0.09 sec) compared to WT (9.32±0.16 sec prothrombin time; p<0.001; n=42). Confocal microscopy, flow cytometry and gene expression studies revealed enhanced vascular oxidative stress (p<0.001; n=6) and a pro-inflammatory endothelium in PON2-/- mice. In line with this, the endogenous interleukin-6 plasma level was increased compared to WT (2-fold) as disclosed by cytokine profiling. Additionally, plasmatic coagulation factors VIII, IX and XI displayed significantly elevated activities in PON2-/- mice (p<0.05; n=10). Further, PON2-/- platelets showed a pro-coagulant activity, due to increased endogenous thrombin potentials triggered by an enhanced phosphatidylserine plasma membrane exposure (p<0.01; n=7). To locate PON2’s dominant effect to either endothelial cells, plasma or platelets, we established bone marrow chimeras and transgenic mice with exclusively endothelial and hematopoietic PON2 expression (Tie2cre-PON2-/-). Coagulation time analyses revealed that the pro-coagulant effect was attenuated in WT chimera with PON2-/- bone marrow (9.22±0.15 sec; n=12) and in Tie2cre-PON2-/- (10.02±0.3 sec; n=23), indicating that much of the effects originates from PON2 functions in the endothelium. Conclusion: We found that PON2 regulates specific pathways of blood coagulation based on a redox-mediated endothelial-dependent modulation of important players in inflammation and hemostasis.

scholarly journals PLATELET-LEUKOCYTE INTERACTIONS : MULTIPLE LINKS BETWEEN INFLAMMATION , BLOOD COAGULATION AND VASCULAR RISK

2010 ◽  
Vol 2 (3) ◽  
pp. e2010023 ◽  
Author(s):  
Chiara Cerletti ◽  
Giovanni De Gaetano ◽  
Roberto Lorenzet
Keyword(s):  
Blood Coagulation ◽  
Vascular Injury ◽  
Cell Function ◽  
Thrombus Formation ◽  
Vascular Wall ◽  
Cell Contact ◽  
Leukocyte Activation ◽  
Activated Platelets ◽  
Bidirectional Relationship ◽  
Inhibitory Molecules

  The aim of this review is to summarize the contribution of platelets and leukocytes and their interactions in inflammation and blood coagulation and its possible relevance in the pathogenesis of  thrombosis. There is some evidence of an association between infection/inflammation and thrombosis. This is likely a bidirectional relationship. The presence of a thrombus may serve as a nidus of infection. Vascular injury indeed promotes platelet and leukocyte activation and thrombus formation and the thrombus and its components facilitate adherence of bacteria to the vessel wall. Alternatively, an infection and the associated inflammation can trigger platelet and leukocyte activation and thrombus formation. In either case platelets and leukocytes co-localize and interact in the area of vascular injury, at sites of inflammation and/or at sites of thrombosis. Following vascular injury, the subendothelial tissue, a thrombogenic surface, becomes available for interaction with these blood cells. Tissue factor, found not only in media and adventitia of the vascular wall, but also on activated platelets and leukocytes, triggers blood coagulation. Vascular-blood cell interactions, mediated by the release of preformed components of the endothelium, is modulated by both cell adhesion and production of soluble stimulatory or inhibitory molecules that alter cell function: adhesion molecules regulate cell-cell contact and facilitate the modulation of biochemical pathways relevant to inflammatory and/or thrombotic processes. 

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