fibrin and Vascular-Calcification

Although mortality rates from coronary heart disease in the western countries have declined in the last few decades, morbidity caused by this disease is increasing and a substantial number of patients still suffer acute coronary syndrome (ACS) and sudden cardiac death. Acute coronary syndrome occurs as a result of myocardial ischaemia and its manifestations include acute myocardial infarction and unstable angina. Culprit plaque morphology in these patients varies from thrombosis with or without coronary occlusion to sudden narrowing of the lumen from intraplaque haemorrhage. The coronary artery plaque morphologies primarily responsible for thrombosis are plaque rupture, and plaque erosion, with plaque rupture being the most common cause of acute myocardial infarction, especially in men. Autopsy data demonstrate that women <50 years of age more frequently have erosion, whereas in older women, the frequency of rupture increases with each decade. Ruptured plaques are associated with positive (expansive) remodelling and characterized by a large necrotic core and a thin fibrous cap that is disrupted and infiltrated by foamy macrophages. Plaque erosion lesions are often negatively remodelled with the plaque itself being rich in smooth muscle cells and proteoglycans with minimal to absence of inflammation. Plaque haemorrhage may expand the plaque rapidly, leading to the development of unstable angina. Plaque haemorrhage may occur from plaque rupture (fissure) or from neovascularization (angiogenesis). Atherosclerosis is now recognized as an inflammatory disease with macrophages and T-lymphocytes playing a dominant role. Recently at least two subtypes of macrophages have been identified. M1 is a pro-inflammatory macrophage while M2 seems to play a role in dampening inflammation and promoting tissue repair. A third type of macrophage, termed by us as haemoglobin associated macrophage or M(Hb) which is observed at site of haemorrhage also can be demonstrated in human atherosclerosis. In order to further our understanding of the specific biological events which trigger plaque instability and as well as to monitor the effects of novel anti-atherosclerotic therapies newer imaging modalities in vivo are needed.

Topics: Acute Coronary Syndrome; Cardiac Imaging Techniques; Chronic Disease; Coronary Artery Disease; Coronary Thrombosis; Female; Fibrin; Hemorrhage; Humans; Macrophages; Male; Necrosis; Plaque, Atherosclerotic; Platelet Aggregation; Risk Factors; Rupture, Spontaneous; Vascular Calcification

Incidence and prevalence of cardiovascular disease (CVD) differ between sexes, and women experience CVD later than men. Changes in fibrin clot lysability are associated with CVD, and the present study addresses sex differences in fibrin clot lysability in asymptomatic middle-aged individuals and the relation to coronary artery calcification (CAC).. Participants free of morbidities and medication, N = 163, were randomly chosen from a national registry among citizens, 50 or 60 years of age, and were followed for 5 years. CAC was determined by the Agatston (Ag) score both at baseline and at follow-up. Based on the changes in Ag, the population was divided into two groups: ΔAg = 0 U or ΔAg > 0 U. Fibrin clot analyses were based on turbidimetric methods.. At baseline, 116 women and 97 men were included; 84 women and 79 men completed the 5-year follow-up (77%). Independently of covariates, women with ΔAg > 0 had reduced mean (SD) fibrin lysability at follow-up, 40.2% (15.9), both in comparison to baseline, 47.8% (20.4), p = 0.001, to women with ΔAg = 0 U, 51.2% (24.5), p = 0.028, and to men with ΔAg > 0 U, 54.4% (21.0), p = 0.002.. Fibrin clot lysability changes over time with considerable sex differences. Women with progression of CAC have reduced fibrin clot lysability compared to men, indicating a sex-specific association between morphological vessel wall changes and fibrin clot lysability.

Topics: Coronary Artery Disease; Coronary Vessels; Female; Fibrin; Fibrinolysis; Humans; Male; Middle Aged; Sex Characteristics; Vascular Calcification

Fibrin sheaths may develop around long-term indwelling central venous catheters (CVCs) and remain in place after the catheters are removed. We evaluated the prevalence, computed tomographic (CT) appearance, and clinical associations of retained fibrin sheaths after CVC removal.. We retrospectively identified 147 adults (77 men and 70 women; mean age 58 y) who underwent CT after CVC removal. The prevalence of fibrin sheath remnants was calculated. Bivariate and multivariate analyses were performed to assess for associations between sheath remnants and underlying diagnoses leading to CVC placement; patients' age and sex; venous stenosis, occlusion, and collaterals; CVC infection; and pulmonary embolism.. Retained fibrin sheaths were present in 13.6% (20/147) of cases, of which 45% (9/20) were calcified. Bivariate analysis revealed sheath remnants to be more common in women than in men [23% (16/70) vs. 5% (4/77), P=0.0018] and to be more commonly associated with venous occlusion and collaterals [30% (6/20) vs. 5% (6/127), P=0.0001 and 30% (6/20) vs. 6% (7/127), P=0.0003, respectively]. Other variables were not associated. Multivariate analysis confirmed the relationship between fibrin sheaths and both female sex (P=0.005) and venous occlusion (P=0.01).. Retained fibrin sheaths were seen on CT in a substantial minority of patients after CVC removal; nearly half of them were calcified. They were more common in women and associated with venous occlusion.

Topics: Adult; Aged; Aged, 80 and over; Catheterization, Central Venous; Catheters, Indwelling; Central Venous Catheters; Device Removal; Female; Fibrin; Humans; Male; Middle Aged; Observer Variation; Retrospective Studies; Sex Distribution; Tomography, X-Ray Computed; Vascular Calcification; Young Adult

Aortic valve stenosis (AS) shares several similarities with atherosclerosis. Factor XIII (FXIII) has been detected within atherosclerotic plaques and may contribute to the development of atherosclerosis via multiple mechanisms. In the current study, we sought to investigate FXIII expression within human stenotic aortic valves and its association with severity of the disease. We prospectively enrolled 91 consecutive patients with AS scheduled for isolated valve replacement. Valvular FXIII subunit A (FXIII-A), fibrin and macrophages expression was evaluated by immunostaining. FXIII-A subunit transcripts and FXIII-A Val34Leu polymorphism was determined by real-time PCR. Plasma FXIII (pFXIII) activity was measured. We demonstrated that the valvular FXIII-A was predominantly expressed on the aortic side of leaflets, colocalized with alternatively activated macrophages (AAM). Areas stained for FXIII-A showed positive correlations with valvular fibrin presence, degree of calcification, pFXIII activity and the severity of AS, reflected by mean and maximum transvalvular gradients (all, p<0.001). The FXIII-A mRNA in the stenotic leaflets was significantly elevated compared to control leaflets. Interestingly, pFXIII activity was also positively correlated with mean (p<0.001) and maximum (p=0.001) transvalvular gradient. The FXIII-A Val34Leu polymorphism did not affect FXIII-A and fibrin expression in AS valves. In conclusion, the study is the first to show abundant expression of FXIII-A at the mRNA and protein levels within human stenotic aortic valves, which is associated with the severity of AS. Our findings might suggest that FXIII in the stenotic valves is presented in AAM and may be involved in the AS progression.

Topics: Aged; Aortic Valve; Aortic Valve Stenosis; Disease Progression; Factor XIII; Female; Fibrin; Gene Expression; Heart Valve Prosthesis Implantation; Humans; Immunohistochemistry; Macrophage Activation; Male; Middle Aged; Plaque, Atherosclerotic; Polymorphism, Genetic; Prospective Studies; Real-Time Polymerase Chain Reaction; RNA, Messenger; Severity of Illness Index; Vascular Calcification