From genetics to response to injury: vascular smooth muscle cells in aneurysms and dissections of the ascending aorta

AbstractVascular smooth muscle cells (vSMCs) play a crucial role in both the pathogenesis of Aneurysms and Dissections of the ascending thoracic aorta (TAAD) in humans and in the associated adaptive compensatory responses, since thrombosis and inflammatory processes are absent in the majority of cases. Aneurysms and dissections share numerous characteristics, including aetiologies and histopathological alterations: vSMC disappearance, medial areas of mucoid degeneration, and extracellular matrix (ECM) breakdown. Three aetiologies predominate in TAAD in humans: (i) genetic causes in heritable familial forms, (ii) an association with bicuspid aortic valves, and (iii) a sporadic degenerative form linked to the aortic aging process. Genetic forms include mutations in vSMC genes encoding for molecules of the ECM or the TGF- β pathways, or participating in vSMC tone. On the other hand, aneurysms and dissections, whatever their aetiologies, are characterized by an increase in wall permeability leading to transmural advection of plasma proteins which could interact with vSMCs and ECM components. In this context, blood-bo rne plasminogen appears to play an important role, because its outward convection through the wall is increased in TAAD, and it could be converted to active plasmin at the vSMC membrane. Active plasmin can induce vSMC disappearance, proteolysis of adhesive proteins, activation of MMPs and release of TGF-β from its ECM storage sites. Conversely, vSMCs could ...
Source: Cardiovascular Research - Category: Cardiology Source Type: research

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CONCLUSION: Our results suggest that PI3P-positive LE/Lys contribute to the membrane growth and proplatelet formation in MKs by their translocation to the cell periphery and fusion with the plasma membrane. PMID: 32056354 [PubMed - as supplied by publisher]
Source: Thrombosis and Haemostasis - Category: Hematology Authors: Tags: J Thromb Haemost Source Type: research
Paradoxical embolism is the translocation of a thrombus originating in the systemic venous circulation into the arterial circulation through a cardiac defect, most commonly a patent foramen ovale (PFO). PFO exists in 15-35% of the adult population. The most common manifestation is cerebrovascular accident; acute limb ischemia is much rarer.
Source: Annals of Vascular Surgery - Category: Surgery Authors: Tags: Case Report Source Type: research
Paradoxical embolism is the translocation of a thrombus originating in the systemic venous circulation into the arterial circulation through a cardiac defect, most commonly a patent foramen ovale (PFO). PFO exists in 15 –35% of the adult population. The most common manifestation is cerebrovascular accident; acute limb ischemia is much rarer.
Source: Annals of Vascular Surgery - Category: Surgery Authors: Tags: Case Report Source Type: research
We present the case of a woman with a severe clinical history of antiphospholipid syndrome and persistent positivity for lupus anticoagulant, IgG anticardiolipin and IgG anti- β2Glycoprotein I antibodies. An acute clinical onset characterized by severe abdominal pain immediately followed by circulatory shock and histological colonic small vessel thrombosis pattern pointed to a diagnosis of ischemic colitis. The subsequent rapid onset of pulmonary alveolitis and heart fai lure associated to subendocardial hypoperfusion led to a diagnosis of definite catastrophic antiphospholipid syndrome (CAPS). Conventional triple the...
Source: Clinical Rheumatology - Category: Rheumatology Source Type: research
CONCLUSIONS: These data demonstrate how endothelial glycocalyx function and functional adaptation to shear is coupled to KLF2-mediated regulation of endothelial glycolysis. PMID: 31826652 [PubMed - as supplied by publisher]
Source: Arteriosclerosis, Thrombosis and Vascular Biology - Category: Cardiology Authors: Tags: Arterioscler Thromb Vasc Biol Source Type: research
Letter by Agbani et al Regarding Article, "Clot Contraction Drives the Translocation of Procoagulant Platelets to Thrombus Surface". Arterioscler Thromb Vasc Biol. 2019 Dec;39(12):e287-e289 Authors: Agbani EO, Hers I, Poole AW PMID: 31770030 [PubMed - in process]
Source: Arteriosclerosis, Thrombosis and Vascular Biology - Category: Cardiology Authors: Tags: Arterioscler Thromb Vasc Biol Source Type: research
Response by Nechipurenko et al to Letter Regarding Article, "Clot Contraction Drives the Translocation of Procoagulant Platelets to Thrombus Surface". Arterioscler Thromb Vasc Biol. 2019 Dec;39(12):e290-e291 Authors: Nechipurenko DY, Mangin PH, Panteleev MA PMID: 31770029 [PubMed - in process]
Source: Arteriosclerosis, Thrombosis and Vascular Biology - Category: Cardiology Authors: Tags: Arterioscler Thromb Vasc Biol Source Type: research
Abstract Platelets harbor the primary reservoir of circulating plasminogen activator inhibitor 1 (PAI-1), but the reportedly low functional activity of this pool of inhibitor has led to debate over its contribution to thrombus stability. Here we analyze the fate of PAI-1 secreted from activated platelets and examine its role in maintaining thrombus integrity. Activation of platelets results in translocation of PAI-1 to the outer leaflet of the membrane, with maximal exposure in response to strong dual agonist stimulation. PAI-1 is found to co-localize in the cap of PS-exposing platelets with its cofactor, vitronec...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
Abstract Protease-activated receptors (PARs) are a family of highly-conserved G protein-coupled receptors (GPCRs), that respond to extracellular proteases via a unique proteolysis-dependent activation mechanism. PAR1 was the first identified member of the receptor family and plays important roles in haemostasis, inflammation and malignancy. The biology underlying PAR1 signalling by its canonical agonist thrombin is well-characterised, however, definition of the mechanistic basis of PAR1 signalling by other proteases, including matrix metalloproteases, activated protein C, plasmin and activated factors VII and X re...
Source: Thrombosis and Haemostasis - Category: Hematology Authors: Tags: J Thromb Haemost Source Type: research
CONCLUSION: Pitavastatin showed lower diabetogenic effects than rosuvastatin in mice that may be mediated by minor attenuations in insulin signaling in adipocytes. PMID: 31527323 [PubMed - as supplied by publisher]
Source: Journal of Atherosclerosis and Thrombosis - Category: Cardiology Tags: J Atheroscler Thromb Source Type: research
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