Association of the Platelet Glycoprotein Ia C807T Gene Polymorphism With Nonfatal Myocardial Infarction in Younger Patients

Blood ◽  
1999 ◽  
Vol 93 (8) ◽  
pp. 2449-2453 ◽  
Author(s):  
S. Santoso ◽  
T.J. Kunicki ◽  
H. Kroll ◽  
W. Haberbosch ◽  
A. Gardemann
Keyword(s):  
Myocardial Infarction ◽  
Odds Ratio ◽  
Type I Collagen ◽  
Strong Association ◽  
Platelet Glycoprotein ◽  
Type I ◽  
Presumptive Diagnosis ◽  
Thrombotic Disease ◽  
Allele Specific ◽  
Artery Disease

Abstract Recently, we have shown that two alleles of the glycoprotein (GP) Ia gene, designated C807 and T807, are associated with low or high platelet GPIa-IIa density and consequently with slower or faster rate of platelet adhesion to type I collagen, respectively. This polymorphism could therefore present a genetic predisposition for the development of thrombotic disease and hemostasis. We investigated the relationship of the GPIa C807T dimorphism to the risk of coronary artery disease (CAD) and myocardial infarction (MI). An allele-specific polymerase chain reaction (PCR) was developed for genotyping of C807T polymorphism. DNA samples from 2237 male patients who underwent coronary angiography on account of coronary heart disease as verified illness or presumptive diagnosis were genotyped. The odds ratio was calculated as an estimate of the relative risk by multiple logistic regression. We found a strong association between the T allele and nonfatal MI among individuals younger than the mean age of 62 years (n = 1,057; odds ratio, 1.57; P = .004). The odds ratio of MI increased for T807 carriers with decreasing age. The highest odds ratio was detected within the youngest 10% of the study sample (<49 years; n = 223; odds ratio, 2.61; P = .009). In contrast, no evidence of an association between C807T dimorphism with CAD was found. Our findings suggest that inherited platelet GP variations might have an important impact on acute thrombotic disease.

Association of the Platelet Glycoprotein Ia C807T Gene Polymorphism With Nonfatal Myocardial Infarction in Younger Patients

Blood ◽  
1999 ◽  
Vol 93 (8) ◽  
pp. 2449-2453 ◽  
Author(s):  
S. Santoso ◽  
T.J. Kunicki ◽  
H. Kroll ◽  
W. Haberbosch ◽  
A. Gardemann
Keyword(s):  
Myocardial Infarction ◽  
Odds Ratio ◽  
Type I Collagen ◽  
Strong Association ◽  
Platelet Glycoprotein ◽  
Type I ◽  
Presumptive Diagnosis ◽  
Thrombotic Disease ◽  
Allele Specific ◽  
Artery Disease

Recently, we have shown that two alleles of the glycoprotein (GP) Ia gene, designated C807 and T807, are associated with low or high platelet GPIa-IIa density and consequently with slower or faster rate of platelet adhesion to type I collagen, respectively. This polymorphism could therefore present a genetic predisposition for the development of thrombotic disease and hemostasis. We investigated the relationship of the GPIa C807T dimorphism to the risk of coronary artery disease (CAD) and myocardial infarction (MI). An allele-specific polymerase chain reaction (PCR) was developed for genotyping of C807T polymorphism. DNA samples from 2237 male patients who underwent coronary angiography on account of coronary heart disease as verified illness or presumptive diagnosis were genotyped. The odds ratio was calculated as an estimate of the relative risk by multiple logistic regression. We found a strong association between the T allele and nonfatal MI among individuals younger than the mean age of 62 years (n = 1,057; odds ratio, 1.57; P = .004). The odds ratio of MI increased for T807 carriers with decreasing age. The highest odds ratio was detected within the youngest 10% of the study sample (<49 years; n = 223; odds ratio, 2.61; P = .009). In contrast, no evidence of an association between C807T dimorphism with CAD was found. Our findings suggest that inherited platelet GP variations might have an important impact on acute thrombotic disease.

Prospective Analysis after Coronary-artery Bypass Grafting: Platelet GP IIIa Polymorphism (HPA-1b /PlA2) Is a Risk Factor for Bypass Occlusion, Myocardial Infarction, and Death

2000 ◽  
Vol 83 (03) ◽  
pp. 404-407 ◽  
Author(s):  
Michael Klein ◽  
Hans Dauben ◽  
Christiane Moser ◽  
Emmeran Gams ◽  
Rüdiger Scharf ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Risk Factor ◽  
Coronary Artery ◽  
Odds Ratio ◽  
Bypass Surgery ◽  
Artery Bypass ◽  
Bypass Grafting ◽  
Hereditary Risk ◽  
Artery Disease

SummaryRecently, we have demonstrated that human platelet antigen 1b (HPA-1b or PlA2) is a hereditary risk factor for platelet thrombogenicity leading to premature myocardial infarction in preexisting coronary artery disease. However, HPA-1b does not represent a risk factor for coronary artery disease itself. The aim of our present study was to evaluate the role of HPA-1b on the outcome in patients after coronaryartery bypass surgery. We prospectively determined the HPA-1 genotype in 261 consecutive patients prior to saphenous-vein coronaryartery bypass grafting. The patients were followed for one year. Among patients with bypass occlusion, myocardial infarction, or death more than 30 days after surgery, the prevalence of HPA-1b was significantly higher than among patients without postoperative complications (60 percent, 6/10, vs. 24 percent, 58/241, p <0.05, odds ratio 4.7). Using a stepwise logistic regression analysis with the variables HPA1b, age, sex, body mass index, smoking (pack-years), hypertension, diabetes, cholesterol and triglyceride concentration, only HPA-1b had a significant association with bypass occlusion, myocardial infarction, or death after bypass surgery (p = 0.019, odds ratio 4.7). This study shows that HPA-1b is a hereditary risk factor for bypass occlusion, myocardial infarction, or death in patients after coronary-artery bypass surgery.

Platelet Glycoprotein Receptor IIIa Polymorphism PlA1/PlA2 and Coronary Risk: a Meta-Analysis

2001 ◽  
Vol 85 (04) ◽  
pp. 626-633 ◽  
Author(s):  
Augusto Di Castelnuovo ◽  
Giovanni de Gaetano ◽  
Maria Benedetta Donati ◽  
Licia Iacoviello
Keyword(s):  
Odds Ratio ◽  
Meta Analysis ◽  
Platelet Glycoprotein ◽  
Published Data ◽  
Coronary Risk ◽  
Gene Encoding ◽  
Glycoprotein Iiia ◽  
Artery Disease ◽  
Revascularization Procedures

SummaryMembrane glycoprotein IIb/IIIa plays a major role in platelet function. The gene encoding the glycoprotein IIIa shows a common polymorphism PlA1/PlA2 that was variably associated with vascular disease. To clarify the role of PlA1/PlA2 polymorphism in coronary risk, a meta-analysis of published data was conducted. Studies were identified both by MEDLINE searches, and hand searching of journals and abstract books.A total of 34 studies for coronary artery disease (CAD), and 6 for restenosis after revascularization were identified, for a total of 9,095 cases and 12,508 controls. In CAD, the overall odds ratio for carriers of the PlA2 allele was 1.10 (95% CI: 1.03 to 1.18), and it was 1.21 (95% CI: 1.05 to 1.38) in subjects younger than 60. Overall odds ratio was 1.31 (95% CI: 1.10 to 1.56) after revascularization procedures.The association of PlA2 status with overall cardiovascular disease in the general population is significant but weak; higher risk has been identified in less heterogeneous subgroups as in the younger cohorts and in the restenosis subset with stents.

Atrial natriuretic peptide, B-type natriuretic peptide, and serum collagen markers after acute myocardial infarction

2004 ◽  
Vol 96 (4) ◽  
pp. 1306-1311 ◽  
Author(s):  
Jarkko Magga ◽  
Mikko Puhakka ◽  
Seppo Hietakorpi ◽  
Kari Punnonen ◽  
Paavo Uusimaa ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Type I Collagen ◽  
Left Ventricular ◽  
Type I ◽  
Amino Terminal ◽  
Collagen Markers ◽  
Atrial Natriuretic

Experimental data suggest that atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) act locally as antifibrotic factors in heart. We investigated the interrelationships of natriuretic peptides and collagen markers in 93 patients receiving thrombolytic treatment for their first acute myocardial infarction (AMI). Collagen formation following AMI, evaluated as serum levels of amino terminal propeptide of type III procollagen, correlated with NH2-terminal proANP ( r = 0.45, P < 0.001), BNP ( r = 0.55, P < 0.001) and NH2-terminal proBNP ( r = 0.50, P < 0.01) on day 4 after thrombolysis. Levels of intact amino terminal propeptide of type I procollagen decreased by 34% ( P < 0.001), and levels of carboxy terminal cross-linked telopeptide of type I collagen (ICTP) increased by 65% ( P < 0.001). ICTP levels correlated with NH2-terminal proBNP ( r = 0.25, P < 0.05) and BNP ( r = 0.28, P < 0.05) on day 4. Our results suggest that ANP and BNP may act as regulators of collagen scar formation and left ventricular remodeling after AMI in humans. Furthermore, degradation of type I collagen is increased after AMI and may be regulated by BNP.

Abstract 17388: Loss of Bone Morphogenetic Protein 9 (BMP9) Limits Survival and Paradoxically Increases Collagen Abundance, but Limits Collagen Cross-Linking in a Murine Model of Acute Myocardial Infarction

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Shreyas Bhave ◽  
Michele Esposito ◽  
Lija Swain ◽  
Xiaoying QIAO ◽  
Gregory Martin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Bone Morphogenetic Protein ◽  
Murine Model ◽  
Cardiac Remodeling ◽  
Type I Collagen ◽  
Cross Linking ◽  
Type I ◽  
Morphogenetic Protein ◽  
Bone Morphogenetic Protein 9 ◽  
Collagen Cross Linking

Myocardial infarction (MI) is a major cause of heart failure (HF). HF is associated with adverse cardiac remodeling that is primarily driven by Transforming growth factor beta (TGFb1) mediated fibrosis and myocyte hypertrophy. We previously reported that loss of bone morphogenetic protein 9 (BMP9) promotes cardiac fibrosis in pressure-overload induced HF. No studies have explored a role for BMP9 in post MI cardiac remodeling. We hypothesize that loss of BMP9 may promote cardiac healing by stabilizing LV scar formation. To test this hypothesis, we subjected whole body BMP9 knockout (-/-) mice to left coronary artery ligation for two weeks followed by PV loop analysis and studied indices of cardiac remodeling. Compared to wild type (WT) controls BMP9-/- mice had significantly lower survival (83% vs 61%, p<0.001, respectively) with a higher rate of cardiac rupture(15% vs 90%). Compared to WT controls, surviving BMP9-/- mice had higher LVEDP, reduced LV dP/dt, and higher lung weight. Compared to WT mice, BMP9-/- mice had significantly higher levels of Type I collagen (2 fold p<0.05). Compared to WT mice, BMP9-/- mice had increased matrix metalloproteinases (MMP)-2 and MMP-9 (2.5 fold p<0.05) activity levels in the LV. Treatment of cultured primary human cardiac fibroblasts with recombinant BMP9 attenuated TGFb1-mediated Type I collagen and MMP-9 protein expression. To assess collagen content and cross-linking, two-photon excitation fluorescence imaging was performed and identified an increase in collagen abundance, but a trend towards lower collagen cross-linking in the LV of BMP9-/- mice compared to WT mice 2 weeks after MI. Our central finding is that loss of BMP9 is associated with reduced survival, increased propensity towards cardiac rupture, and increased LV collagen abundance, but reduced collagen integrity in a murine model of acute MI. These identify a potentially important functional role for BMP9 in post-infarct cardiac remodeling.

Osteogenesis imperfecta in Three Dogs from a Single Litter

2000 ◽  
Vol 13 (01) ◽  
pp. 23-27
Author(s):  
J. J. deHaan ◽  
J. N. Peck ◽  
Bonnie Campbell ◽  
Pamela Ginn ◽  
Lynette Phillips ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Type I Collagen ◽  
Type I ◽  
Fibroblast Cells ◽  
Pathological Fractures ◽  
Presumptive Diagnosis ◽  
Cultured Skin ◽  
Pathologic Features ◽  
History Of ◽  
Collagen Analysis

SummaryThree American Cream puppies from a litter of six were admitted for evaluation and treatment of lameness caused by multiple pathological fractures. Because of a poor prognosis, all three of the affected dogs were ultimately euthanatized. Based on the histopathological findings of the bones and a collagen analysis from cultured skin fibroblast cells which confirmed the presence of abnormal type I collagen, the presumptive diagnosis was osteogenesis imperfecta. In humans, more than 90% of the cases of osteogenesis imperfecta are caused by defects in type I collagen (11). Osteogenesis imperfecta has rarely been described in animals and none of the previous reports document the disease in more than one dog from a single litter.Three American Cream puppies from a litter of six developed multiple pathologic features without a history of trauma. A diagnosis of osteogenesis imperfecta was made based on histopathology and results of type I collagen analysis from cultured skin fibroblasts.

scholarly journals Type I Collagen Cleavage Is Essential for Effective Fibrotic Repair after Myocardial Infarction

2011 ◽  
Vol 179 (5) ◽  
pp. 2189-2198 ◽  
Author(s):  
Zengxuan Nong ◽  
Caroline O'Neil ◽  
Ming Lei ◽  
Robert Gros ◽  
Alanna Watson ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Type I Collagen ◽  
Type I

scholarly journals Biomechanical assessment of remote and postinfarction scar remodeling following myocardial infarction

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mihaela Rusu ◽  
Katrin Hilse ◽  
Alexander Schuh ◽  
Lukas Martin ◽  
Ioana Slabu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Type I Collagen ◽  
De Novo ◽  
Heart Function ◽  
Type Iii Collagen ◽  
Type I ◽  
Compensatory Mechanisms ◽  
Biomechanical Assessment ◽  
Type V

AbstractThe importance of collagen remodeling following myocardial infarction (MI) is extensively investigated, but little is known on the biomechanical impact of fibrillar collagen on left ventricle post-MI. We aim to identify the significant effects of the biomechanics of types I, III, and V collagen on physio-pathological changes of murine hearts leading to heart failure. Immediately post-MI, heart reduces its function (EF = 40.94 ± 2.12%) while sarcomeres’ dimensions are unchanged. Strikingly, as determined by immunohistochemistry staining, type V collagen fraction significantly grows in remote and scar for sustaining de novo-types I and III collagen fibers’ assembly while hindering their enzymatic degradation. Thereafter, the compensatory heart function (EF = 63.04 ± 3.16%) associates with steady development of types I and III collagen in a stiff remote (12.79 ± 1.09 MPa) and scar (22.40 ± 1.08 MPa). In remote, the soft de novo-type III collagen uncoils preventing further expansion of elongated sarcomeres (2.7 ± 0.3 mm). Once the compensatory mechanisms are surpassed, the increased turnover of stiff type I collagen (>50%) lead to a pseudo-stable biomechanical regime of the heart (≅9 MPa) with reduced EF (50.55 ± 3.25%). These end-characteristics represent the common scenario evidenced in patients suffering from heart failure after MI. Our pre-clinical data advances the understanding of the cause of heart failure induced in patients with extended MI.

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