Timp-1

Lindsay, Mitchell; Maxwell, Paul R.; Dunn, Francis G.

doi:10.1161/01.hyp.0000024573.17293.23

Cited by 169 publications

(31 citation statements)

References 39 publications

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“…TIMP-1 was significantly elevated in patients with diastolic dysfunction and correlated with markers of diastolic filling, namely E:A ratio and E Dec. A plasma TIMP-1 level of [500 ng/ml had a specificity of 97% and a positive predictive value of 96% in predicting diastolic dysfunction [25].…”

Section: Pathophysiology Of Ecm Remodelling In Hypertension and Hfmentioning

confidence: 93%

Extracellular matrix fibrotic markers in heart failure

2009

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Given the importance of fibrous tissue in leading to myocardial dysfunction, non-invasive assessment of fibrosis could prove a clinically useful tool in heart failure (HF) patients. Biomarkers may be used for early detection of otherwise subclinical disease, diagnostic assessment of an acute or chronic clinical syndrome, risk stratification of patients with a suspected or confirmed diagnosis, selection of an appropriate therapeutic intervention and monitoring the response to therapy. Extracellular matrix (ECM) biomarkers in HF are promising biomarkers. They are able to detect early changes in heart and large vessel structure and function and transition to HF. High ECM biomarker levels have been associated with poor outcome. The ability of treatment to reduce myocardial fibrosis in HF patients may be monitored by the measurement of various serum peptides arising from the metabolism of collagen types. Biomarkers may be selectively influenced by pharmacological agents.

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Section: Pathophysiology Of Ecm Remodelling In Hypertension and Hfmentioning

confidence: 93%

Extracellular matrix fibrotic markers in heart failure

2009

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“…16 When examined from a biophysical-mechanical basis, it is clear that the ECM contributes to stiffness properties of muscle in general and holds particular relevance to the myocardium. 9–12,17,19,39,42,44,63,71–73 For example, correlative studies, such as those reported by Borg et al, demonstrated that species-specific differences in the structure and composition of fibrillar collagen was associated with changes in myocardial stiffness. 70 In clinical studies of LV hypertrophy secondary to a prolonged pressure overload, significant collagen accumulation was directly associated with indices reflective of increased LV myocardial stiffness.…”

Section: Myocardial Extracellular Matrix Redefined and Mmp Relevancementioning

confidence: 99%

“…39–44,56,108,112–114 While the sources and origins of changes in peripheral levels of MMPs can be multifactorial, clinical studies have provided evidence that profiling MMPs as well as TIMPs can hold diagnostic and prognostic significance in the context of HF. 44,112 As basic science studies on the biological roles of specific MMP types continues, it is likely that a refined set of MMP measurements from a peripheral blood sample would be useful biomarkers for identifying those patients at risk for more rapid and progressive LV remodeling and the development of HF.…”

Section: Mmp Proteolysis and Profibrosis: Two Sides Of The Same Coinmentioning

confidence: 99%

Membrane-Associated Matrix Proteolysis and Heart Failure

Spinale

Janicki²,

Zile³

2013

Circulation Research

142

138

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The extracellular matrix (ECM) is a complex entity containing a large portfolio of structural proteins, signaling molecules, and proteases. Changes in the overall integrity and activational state of these ECM constituents can contribute to tissue structure and function, which is certainly true of the myocardium. Changes in the expression patterns and activational states of a family of ECM proteolytic enzymes, the matrix metalloproteinases (MMPs), have been identified in all forms of LV remodeling and can be a contributory factor for the progression to heart failure. However, new clinical and basic research has identified some surprising and unpredicted changes in MMP profiles in LV remodeling processes, such as with pressure or volume overload, as well as with myocardial infarction. From these studies, it has become recognized that proteolytic processing of signaling molecules by certain MMP types, particularly the transmembrane MMPs, may actually facilitate ECM accumulation as well as modulate fibroblast transdifferentiation – both critical events in adverse LV remodeling. Based upon the ever increasing substrates and diversity of biological actions of MMPs, it is likely that continued research regarding the relationship of LV remodeling to this family of proteases will yield new insights into the ECM remodeling process itself as well as new therapeutic targets.

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“…Experimentally and in humans, EH is associated with interstitial fibrosis of the myocardium, the presumed basis for diastolic dysfunction [20]. Myocardial stiffness and metabolic active relaxation are the main determinants of LV diastolic function.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, experimental studies provided convincing evidence that overactivation of the renin-angiotensin-aldosterone system, or part of it, may accelerate myocardial mass increase and fibrosis, even when the haemodynamic load is low [16,17,18,19,20]. Moreover, it was proposed that slightly elevated aldosterone levels still in the physiological range may predict the risk of developing hypertension [21].…”

Section: Introductionmentioning

confidence: 99%

Diastolic Dysfunction Is Associated with Insulin Resistance, but Not with Aldosterone Level in Normotensive Offspring of Hypertensive Families

et al. 2008

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Background and Aims: We investigated left ventricular (LV) morphology and function in association with insulin level/insulin resistance (IR) and aldosterone level in normotensive offspring of subjects with essential hypertension (familial trait, FT). Methods: The study encompassed 76 volunteers of whom 44 were normotensive with FT (aged 28–39 years) and 32 age-matched controls without FT. LV mass and function were measured using conventional echocardiography and tissue Doppler imaging. LV diastolic function was reported as peak septal annular velocities (E_m and E_m/A_m ratio) in tissue Doppler imaging. Fasting insulin and aldosterone were determined. Results: In subjects with FT, the LV mass was higher than in controls (92.14 ± 24.02 vs. 70.08 ± 20.58 g; p < 0.001). The study group had a worse LV diastolic function than control subjects (lower E_m and E_m/A_m ratio; p < 0.001). In subjects with FT, the E_m/A_m ratio was independently associated with IR (partial p = 0.029 in multivariate model, R² = 0.51), but not with LV mass. The aldosterone level was comparable in both groups. Conclusions: In normotensive individuals with FT, LV morphological and functional abnormalities were found. LV dysfunction but not an increase in LV mass is associated with IR. The aldosterone level is probably not responsible for the development of early hypertensive heart disease.

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Timp-1

Cited by 169 publications

References 39 publications

Extracellular matrix fibrotic markers in heart failure

Extracellular matrix fibrotic markers in heart failure

Membrane-Associated Matrix Proteolysis and Heart Failure

Diastolic Dysfunction Is Associated with Insulin Resistance, but Not with Aldosterone Level in Normotensive Offspring of Hypertensive Families

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