Prolidase activity in patients with coronary artery aneurysm.

Decreased collagen biosynthesis and increased collagenolysis may induce aneurysmal progress in arterial walls. Prolidase plays a role in collagen synthesis. In this study, we sought to evaluate whether there is a correlation between nonatherosclerotic coronary artery aneurysms (CAAs) and prolidase activity. A total of 174 CAAs were diagnosed in 144 (2.1%) patients among 6845 coronary angiographies performed between 2009 and 2012. In all, 23 (15.9%) patients had nonatherosclerotic aneurysms. Prolidase activity was compared to the results of 19 healthy volunteers with normal coronary arteries. Demographic parameters were similar between the groups. Mean prolidase activity was 241.6 ± 54.4 mU/mL in the coronary aneurysm group and 730.3 ± 243.1 mU/mL in the control group (P < .001). The incidence of CAAs ranges between 0.3% and 5.3% in the general population. Decreased prolidase activity may reduce collagen biosynthesis that may contribute to aneurysm formation.

Cell distribution differences of matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1 in patients with Kawasaki disease.

The interaction of matrix metalloproteinase (MMP)-9 and tissue inhibitor of matrix metalloproteinase-1 has been implicated in the formation of coronary aneurysms in Kawasaki disease. MMP-9 and tissue inhibitor of matrix metalloproteinase-1 were distributed predominantly in the granulocytes and platelets, respectively, in patients with Kawasaki disease. The plasma values of MMP-9 correlated positively with the circulating neutrophil count. Inhibiting the activity of granulocytes and maintaining the platelet activity might prevent coronary aneurysms.

Neutrophil gelatinase-associated lipocalin levels in isolated coronary artery ectasia.

BACKGROUND: The pathophysiology of coronary artery ectasia (CAE) is still unknown. Inflammation and degradation of connective tissue may have a role in the development of coronary ectasia. In the present study, the authors examined neutrophil gelatinase-associated lipocalin (NGAL) levels in isolated CAE patients. METHODS: Thirty-five patients with isolated CAE (25 males; mean age, 59±10 years) and 35 age- and sex-matched healty volunteers (22 males; mean age, 57±11 years) who had been shown to have normal coronary arteries were included in the study. Basal characteristics were recorded. Serum NGAL levels were determined with an enzyme-linked immunosorbent assay kit. RESULTS: NGAL levels were significantly higher in the isolated CAE group than in the control group (65.1±13 vs 53.7±19 ng/mL; P=0.006). There were also significant difference in NGAL levels according to the number of ectatic coronary arteries (58.1±13, 70.9±9, and 71.1±11 ng/mL for 1, 2, and 3 arteries, respectively; P=0.015). Level of NGAL was lowest in patients who have only 1 ectatic coronary artery. CONCLUSION: Serum NGAL levels increased in patients with isolated CAE, and NGAL may play a crucial role in the development and/or progression of coronary artery ectasia.

Transgenic expression of matrix metalloproteinase-2 induces coronary artery ectasia.

Coronary artery ectasia (CAE) is generally diagnosed in patients undergoing arteriography for presumptive atherosclerotic coronary artery disease. CAE is commonly considered as a variant of atherosclerotic disease; however, recent studies suggest that CAE is the result of a systemic vascular disorder. There is increasing evidence that aneurysmal vascular disease is a systemic disorder characterized by enhanced expression of pro-inflammatory cytokines and increased synthesis of enzymes capable of degrading elastin and other components of the vascular wall. Matrix metalloproteinase-2 degrades a number of extracellular substrates, including elastin and has been shown to play a critical role in the development of abdominal aortic aneurysms. This study characterizes the development of CAE in a unique murine transgenic model with cardiac-specific expression of active MMP-2. Transgenic mice were engineered to express an active form of MMP-2 under control of the α-myosin heavy chain promoter. Coronary artery diameters were quantified, along with studies of arterial structure, elastin integrity and vascular expression of the MMP-2 transgene. Latex casts quantified total coronary artery volumes and arterial branching. Mid-ventricular coronary luminal areas were increased in the MMP-2 transgenics, coupled with foci of aneurysmal dilation, ectasia and perivascular fibrosis. There was no evidence for atherogenesis. Coronary vascular elastin integrity was compromised and coupled with inflammatory cell infiltration. Latex casts of the coronary arteries displayed ectasia with fusiform dilatation. The MMP-2 transgenic closely replicates human CAE and supports a critical and initiating role for this enzyme in the pathogenesis of this disorder.

Matrix metalloproteinases and inflammatory markers in coronary artery ectasia: their relationship to severity of coronary artery ectasia.

OBJECTIVE: Although underlying mechanisms of coronary artery ectasia (CAE) are clearly unknown, destruction of extracellular matrix may be responsible for the ectasia formation. Thus, we investigated the role of matrix metalloproteinases (MMP), tissue inhibitor of matrix metalloproteinases (TIMP-1), and inflammatory markers [high-sensitive C-reactive protein, interleukins (ILs)] in CAE patients. METHODS: This study consisted of 28 consecutive CAE patients, 27 obstructive coronary artery disease (CAD) patients, and 22 controls with normal coronary arteries undergoing cardiac catheterization. Plasma levels of MMP-3, MMP-9, TIMP-1, and inflammatory markers were measured. RESULTS: Plasma level of MMP-3 was significantly higher in CAE patients compared with both CAD patients and controls (17.2+/-6.1, 11.2+/-3.2, and 9.2+/-3.4 ng/ml, respectively, both P=0.001) and so did MMP-9 level (27.4+/-5.9, 24.8+/-4.4, and 20.6+/-4.6 ng/ml, respectively, both P<0.05). IL-6 level was also higher in CAE patients than in controls (60.9+/-22.1 vs. 36.1+/-21.5 pg/ml, P=0.001) but were comparable in CAE and CAD patients. Plasma high-sensitive C-reactive protein, IL-1, and TIMP-1 levels were similar in three groups. MMP-3 levels correlated with diffuse (r=0.46, P=0.01) and multivessel ectasia (r=0.45, P=0.02). CONCLUSION: Our results suggest that the increased level of MMP-3, MMP-9, and IL-6 may be responsible for ectasia formation in patients with CAE.

[Matrix metalloproteinase-1 expression in the circulation of patients with Kawasaki disease and its role in the pathogenesis of coronary artery lesions].

OBJECTIVE: Kawasaki disease (KD) is an acute and self-limited systemic vasculitis syndrome of unknown origin that mainly affects small and medium-sized arteries, particularly the coronary arteries, which is followed by aneurysm formation. Increased levels of matrix metalloproteinase-1 (MMP-1) have been detected in aortic aneurysms in adults, suggesting an important role of MMP-1 in arterial wall destruction and resultant aneurysm formation. The aim of this study was to investigate the potential role of MMP-1 in the pathogenesis of coronary artery lesions in patients with KD. METHODS: Forty patients with KD, including 23 patients without coronary artery lesions (CAL) and 17 patients with CAL, as well as age-matched 10 febrile and 10 healthy afebrile controls were studied. The duration of KD was divided into three phases: the acute phase, the subacute phase and the convalescent phase. Enzyme-linked immunosorbent assay was used to detect the protein levels of MMP-1 in the sera. MMP-1 mRNA expression in the circulating leucocytes was studied using reverse transcription-polymerase chain reaction. RESULTS: Levels of MMP-1 protein in serum and MMP-1 mRNA expression in the leucocytes were significantly elevated at the acute phase in the two groups of KD patients (CAL group: 14.91 +/- 3.88 ng/ml and 0.89 +/- 0.15 ng/ml; NO-CAL group: 11.27 +/- 3.28 ng/ml and 0.77 +/- 0.14, respectively), compared with febrile (7.05 +/- 1.98 ng/ml and 0.45 +/- 0.12 ng/ml, respectively) and afebrile (5.13 +/- 1.20 ng/ml and 0.29 +/- 0.12 ng/ml, respectively) controls (P < 0.01). Furthermore, MMP-1 protein and MMP-1 mRNA levels were significantly higher in KD patients with CAL than in KD patients without CAL (P < 0.05). There was a significantly positive correlation between the serum protein level of MMP-1 at the acute phase of KD and the circulating leucocytes counts (r = 0.750, P < 0.01). The MMP-1 serum protein level and mRNA expression in the leucocytes at the acute phase of the two KD groups decreased obviously from the subacute through the convalescent phases (P < 0.05 or P < 0.01). CONCLUSION: The expression of MMP-1 at the acute phase of KD was significantly elevated, especially in KD patients with CAL. MMP-1 might be involved in the formation of coronary artery lesions and pathogenesis of KD.

Systemic arterial expression of matrix metalloproteinases 2 and 9 in acute Kawasaki disease.

OBJECTIVE: Coronary artery aneurysms are the major complication of Kawasaki disease (KD). Matrix metalloproteinases (MMPs) regulate remodeling and degradation of the extracellular matrix. We hypothesized that MMP-9 expression is increased in acute KD aneurysms when compared with KD nonaneurysmal arteries and arteries from control children. METHODS AND RESULTS: MMP-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-2 were immunolocalized in coronary arteries from children with fatal acute KD and controls. In KD coronary aneurysms, MMP-2 expression was prominent in the thickened neointima and in endothelial cells of new capillaries in areas of angiogenesis. MMP-9 was absent in control coronary arteries but was expressed in coronary artery aneurysms, nonaneurysmal coronary and noncoronary arteries, and cardiac nerves in acute KD, without an increase in TIMP-1 expression. CONCLUSIONS: MMP-2 likely participates in remodeling of the arterial wall in acute KD, particularly in the processes of neointimal proliferation and angiogenesis. MMP-9 may play a role in the development of coronary aneurysms, but its expression is not confined to aneurysmal arteries. Systemic arterial expression of MMP-9 in acute KD, even in the absence of inflammatory changes in the vessel, suggests induction by a circulating factor, or possibly by an infectious agent with tropism for arterial tissue.

[MB isoenzyme of myocardial creatino-kinase: activity curves in the blood, after ischemic cardiopathy surgery]. / Isoenzima MB da creatino-quinase miocárdica (CK-MB): curvas de actividade no soro, após cirurgia de cardiopatia isquémica.

OBJECTIVE: To determine the curve of cardiac creatine-kinase (MB-CK) plasma activity, in patients with coronary heart disease who were submitted to Coronary Artery Bypass Graft (CABG) and/or aneurysmectomy, in order to evaluate the degree of a eventual myocardial lesion occurring during the first 72 hours after surgery. DESIGN: Assay of the plasma MB-CK activity and of the 12 lead electrocardiogram (EGC) during the first 72 hours after surgery. SETTING: Patients undergoing surgery in a Department of Cardiac Surgery. PATIENTS: 49 consecutive patients included in 2 groups: Group A: 38 pts submitted to CABG. Group B: 11 pts submitted to aneurysmectomy (6 of them with simultaneous CABG). INTERVENTIONS: Determination of plasma MB-CK activity and execution of 12 lead EGC before surgery and at 0, 6, 12, 24, 36 and 72 hours after surgery. RESULTS: Using as a reference the MB-CK values in a control group undergoing surgery for either aortic or mitral valvulopathy, the patients in group A were subdivided: Group A1: 25 pts which curves of MB-CK activity were similar to the control group; none showed sign of myocardial infarction in the EGC. Group A2: 13 pts which curves of MB-CK activity showed a increased value when compared to controls (at least, two Standard Deviation above the medium control value). In 6 of them the EGC were compatible with acute myocardial infarction. Group B patients were also divided in 2 subgroups: Group B1: 10 pts with a similar MB-CK activity to the control group. Group B2: 1 patient with MB-CK activity similar to the patients in Group A2 and whose EKG showed a pattern of "the new" myocardial infraction. CONCLUSIONS: The method used in our work allowed us to define a MB-CK activity curve that translates the expected variability after surgery in patients submitted to CABG and/or aneurysmectomy. This curve allows the distinction between myocardial lesion due to surgical aggression and a ischemic lesion. The EGC although a method with high specificity has apparently a low sensitivity for the detection of myocardial necrosis after CABG. The aneurysmectomy "per se" does not influence the MB-CK activity.