Cardiopulmonary bypass induces the synthesis and release of matrix metalloproteinases

Joffs, Cassandra; Gunasinghe, Himali R.; Multani, Marlina M.; Dorman, B. Hugh; Kratz, John M.; Crumbley, Arthur J.; Crawford, Fred A.; Spinale, Francis G.

doi:10.1016/s0003-4975(01)02442-0

Cited by 54 publications

(77 citation statements)

References 22 publications

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“…42,43 On that basis, our current findings led us to consider that the concentrations of circulating MMPs and TIMPs may reflect the histopathological events occurring in the failing heart of HCM patients.…”

Section: Study Limitationsmentioning

confidence: 71%

Increased Circulating Matrix Metalloproteinase-2 in Patients With Hypertrophic Cardiomyopathy With Systolic Dysfunction

Noji

Shimizu

Ino

et al. 2004

Circ J

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ypertrophic cardiomyopathy (HCM) is characterized by disproportionate left ventricular (LV) hypertrophy and LV diastolic dysfunction. However, some patients with HCM develop LV wall thinning associated with LV dilatation and systolic dysfunction. [1][2][3][4][5][6][7] The pathological features reveal that such patients have myocardium with marked fibrosis and abnormal collagen matrices. 8 Evidence suggests that LV myocardial collagen matrix disorganization and changes in the fibrillar collagen network contribute to the progression of LV dilatation and dysfunction. 9,10 Matrix disorganization in LV dilatation has, in turn, been attributed to enhanced collagen degradation Circulation Journal Vol.68, April 2004 through changes in the concentrations of matrix metalloproteinases (MMPs) or their tissue inhibitors (TIMPs). [11][12][13] It has been suspected that the MMPs play an important role in tissue remodeling in both normal and pathological conditions. 14-22 Enhanced activity of MMPs could lead to increased collagen turnover and has been reported in idiopathic dilated cardiomyopathy (DCM), 19 tachycardiainduced heart failure 12,20 and pressure-overload hypertrophy. 13 Elevated concentrations of the serum markers of collagen turnover have also been reported in patients with idiopathic DCM. 21 Soejima et al showed a significant negative correlation between the concentration of serum MMP-1 and LV ejection fraction (LVEF). 22 Collectively, these findings suggest that changes in collagen metabolism may be associated with LV remodeling and the progression of LV systolic dysfunction in patients with HCM. However, the exact details and sequence of clinicopathological events remain uncertain.The present study was conducted in order to test the hypothesis that circulating MMPs and TIMPs may be altered in patients with HCM with systolic dysfunction and may be associated with LV remodeling in HCM. Methods and ResultsEnzyme-linked immunoassays were used to measure the plasma concentrations of MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2 in 11 patients with HCM accompanied by systolic dysfunction (fractional shortening (FS) <25%, group A), 17 patients with HCM who had preserved systolic function (FS ≥25%, group B), and 50 age-matched clinically healthy control subjects (mean age: 57 years). The concentration of MMP-2 in group A was significantly higher than in group B and the control subjects (1,124±84, 792±49, 809±26 ng/ml, respectively), whereas there was no significant difference between group B and the control subjects. MMP-2 concentrations significantly increased as the New York Heart Association functional class increased in patients with HCM. TIMP-2 was also significantly higher in group A patients than in group B and the control subjects (45.3±4.7, 34.6±2.2, 33.7±1.8 ng/ml, respectively), but there was no difference between group B and control subjects. TIMP-1 was significantly higher in HCM patients than in control subjects. MMP-3 and MMP-9 concentrations did not differ among the 3 groups. Both MMP-2 and TIMP-2 correlat...

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Section: Study Limitationsmentioning

confidence: 71%

Increased Circulating Matrix Metalloproteinase-2 in Patients With Hypertrophic Cardiomyopathy With Systolic Dysfunction

Noji

Shimizu

Ino

et al. 2004

Circ J

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“…Finally, this clinical study demonstrated a net increase in relative MMP-2 and MMP-9 zymographic levels in plasma samples obtained directly from the coronary sinus. In the same clinical context of brief ischemia-reperfusion secondary to cardiac surgery, a past study by this laboratory demonstrated an absolute increase in pro-MMP-2 release across the myocardial circulatory bed using a quantitative immunoassay approach (181). As shown in Figure 10, a greater increase in pro-MMP-2 was released from the coronary sinus than that entering the coronary arteries indicative of de novo myocardial synthesis and release of pro-MMP-2.…”

Section: Human-based Studiesmentioning

confidence: 90%

“…Thus oxidative stress and the formation of ROS cause the activation of MMPs through two primary mechanisms: posttranslational modification of pro-MMPs to an active form which will be discussed in a subsequent section, and the formation of transcriptional complexes which will yield newly formed MMP species (121,303,387,401,402,478,483). Studies in several laboratories have demonstrated a direct relationship between the formation of ROS and the induction of MMPs in the context of ischemia/reperfusion and cardiac surgery (181,235,268,269). Moreover, in vitro studies have demonstrated that direct exposure of ROS will induce MMP release (19,72,536).…”

Section: Additional Biological Pathways To Mmp Transcriptionmentioning

confidence: 99%

Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function

Spinale¹

2007

Physiological Reviews

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It is now becoming apparent that dynamic changes occur within the interstitium that directly contribute to adverse myocardial remodeling following myocardial infarction (MI), with hypertensive heart disease and with intrinsic myocardial disease such as cardiomyopathy. Furthermore, a family of matrix proteases, the matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs), has been recognized to play an important role in matrix remodeling in these cardiac disease states. The purpose of this review is fivefold: 1) to examine and redefine the myocardial matrix as a critical and dynamic entity with respect to the remodeling process encountered with MI, hypertension, or cardiomyopathic disease; 2) present the remarkable progress that has been made with respect to MMP/TIMP biology and how it relates to myocardial matrix remodeling; 3) to evaluate critical translational/clinical studies that have provided a cause-effect relationship between alterations in MMP/TIMP regulation and myocardial matrix remodeling; 4) to provide a critical review and analysis of current diagnostic, prognostic, and pharmacological approaches that utilized our basic understanding of MMP/TIMPs in the context of cardiac disease; and 5) most importantly, to dispel the historical belief that the myocardial matrix is a passive structure and supplant this belief that the regulation of matrix protease pathways such as the MMPs and TIMPs will likely yield a new avenue of diagnostic and therapeutic strategies for myocardial remodeling and the progression to heart failure.

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“…Third, analyses relating plasma MMP-9 to echocardiographic measures presuppose that plasma levels correlate with myocardial levels and that the heart is an important source of circulating MMP-9. 51 Fourth, plasma MMP-9 was below the detection limit of the standardized assay in 80% of our sample; as a result, statistical analyses were constrained by the use of MMP-9 as a binary variable. As our sample was predominantly white, generalizability to other ethnic groups is limited.…”

Section: Limitations and Strengthsmentioning

confidence: 98%

Relations of Plasma Matrix Metalloproteinase-9 to Clinical Cardiovascular Risk Factors and Echocardiographic Left Ventricular Measures

et al. 2004

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Background-Plasma levels of matrix metalloproteinase-9 (MMP-9), a key determinant of extracellular matrix degradation, are increased in heart failure and in acute coronary syndromes. We investigated cross-sectional relations of plasma MMP-9 to vascular risk factors and echocardiographic left ventricular (LV) measurements. Methods and Results-We studied 699 Framingham Study participants (mean age, 57 years; 58% women), free of heart failure and previous myocardial infarction, who underwent routine echocardiography. We examined sex-specific distributions of LV internal dimensions (LVEDD) and wall thickness (LVWT) and sampled persons with both LVEDD and LVWT below the sex-specific median (referent, nϭ299), with increased LVEDD (LVEDD Ն90th percentile, nϭ204) and increased LVWT (LVWT Ն90th percentile, nϭ221) in a 3:2:2 ratio. Plasma MMP-9 was detectable in 138 persons (20%). In multivariable models, increasing heart rate (OR per SD, 1.41; 95% CI, 1.17 to 1.71) and antihypertensive treatment (OR, 1.63; 95% CI, 1.06 to 2.50) were key clinical correlates of detectable plasma MMP-9. In multivariable-adjusted models, detectable plasma MMP-9 was associated with increased LVEDD (OR, 2.84; 95% CI, 1.13 to 7.11), increased LVWT (OR, 2.54; 95% CI, 1.00 to 6.46), and higher LV mass (Pϭ0.06) in men but not in women (OR for increased LVEDD, 1.37; 95% CI, 0.54 to 3.46; for increased LVWT, 0.99; 95% CI, 0.39 to 2.52; Pϭ0.59 for LV mass). Conclusions-In our community-based sample, detectable plasma MMP-9 levels were associated with increased LV diastolic dimensions and increased wall thickness in men. These observations indicate that plasma MMP-9 level may be a marker for cardiac extracellular matrix degradation, a process involved in LV remodeling.

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Cardiopulmonary bypass induces the synthesis and release of matrix metalloproteinases

Cited by 54 publications

References 22 publications

Increased Circulating Matrix Metalloproteinase-2 in Patients With Hypertrophic Cardiomyopathy With Systolic Dysfunction

Increased Circulating Matrix Metalloproteinase-2 in Patients With Hypertrophic Cardiomyopathy With Systolic Dysfunction

Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function

Relations of Plasma Matrix Metalloproteinase-9 to Clinical Cardiovascular Risk Factors and Echocardiographic Left Ventricular Measures

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