Molecular Imaging for Efficacy of Pharmacologic Intervention in Myocardial Remodeling

Borne, Susanne W.M. van den; Isobe, Satoshi; Zandbergen, H. Reinier; Li, Peng; Petrov, Artiom; Wong, Nathan D.; Fujimoto, Shinichiro; Fujimoto, Ai; Løvhaug, Dagfinn; Smits, J. F. M.; Daemen, Mat J.A.P.; Blankesteijn, W. Matthijs; Reutelingsperger, Chris; Zannad, Faı̈ez; Narula, Navneet; Vannan, Mani A.; Pitt, Bertram; Hofstra, Leonard; Narula, Jagat

doi:10.1016/j.jcmg.2008.11.011

Cited by 62 publications

(48 citation statements)

References 33 publications

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“…In the subsequent study, 99m Tc-CRIP imaging was used to evaluate the therapeutic effects of captopril, losartan, and spironolactone, individually or in combination. 62 Radiotracer infarct uptake of 2.3% injected dose per gram of tissue (%ID/g) in untreated animals reduced to 1.7% ID/g by single treatment using any of the 3 drugs and further reduced by a combination of 2 or 3 drugs (1.31% and 1.16% ID/g, respectively). As in the previous study, radiotracer uptake correlated with the extent of myofibroblast accumulation and the presence of newly formed collagen fibers; the treatment did not reduce collagen formation in the scar.…”

Section: Imaging Myofibroblasts and Rasmentioning

confidence: 99%

Molecular Imaging of the Cardiac Extracellular Matrix

Haas

Arbustini

Fuster

et al. 2014

Circulation Research

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Section: Imaging Myofibroblasts and Rasmentioning

confidence: 99%

Molecular Imaging of the Cardiac Extracellular Matrix

Haas

Arbustini

Fuster

et al. 2014

Circulation Research

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“…Baseline strain (␤ ϭ 0.47, p Ͻ 0.0001), spironolactone therapy (␤ ϭ Ϫ0.38, p Ͻ 0.0001), and change in PICP level (␤ ϭ Ϫ0. 19, p Ͻ 0.03) were independently associated with LV systolic function improvement (increase in strain). Correlates of LV diastolic function improvement (increase in early diastolic mitral annular velocity) were baseline early diastolic mitral annular velocity (␤ ϭ 0.47, p Ͻ 0.0001), spironolactone therapy (␤ ϭ Ϫ0.…”

mentioning

confidence: 93%

A Randomized Study of the Beneficial Effects of Aldosterone Antagonism on LV Function, Structure, and Fibrosis Markers in Metabolic Syndrome

Kosmala

Przewlocka‐Kosmala

Szczepanik-Osadnik

et al. 2011

JACC: Cardiovascular Imaging

116

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“…14 Preclinical studies have shown feasibility of visualizing avb 3 integrin 15,16 (on myofibroblasts), angiotensin-converting enzyme (ACE), 17 angiotensin II receptor type 1 (AT1), 18 and coagulation factor XIII. 19 Although initial small scale clinical pilot studies have been performed for some of these tracers, [20][21][22] no definitive studies have been performed.…”

Section: See Related Article Pp 1114-1123mentioning

confidence: 99%

Playing slot to hitting the jackpot in molecular imaging: On probability of uncovering subcellular pathogenesis vs achieving clinical applicability

Haas

Narula

2018

Journal of Nuclear Cardiology

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Myocardial infarction (MI), despite optimal reperfusion therapy, results in substantial loss of muscle tissue through apoptosis and necrosis. The repair process post MI is traditionally divided into consecutive and partly overlapping inflammation, proliferation, and maturation phases. The initial phase is characterized by infiltration of inflammatory cells removing cellular debris, and formation of new blood vessels. Matrix metalloproteinases (MMP) and other proteolytic enzymes secreted by inflammatory cells facilitate these processes. During the proliferatory phase, fibroblasts transdifferentiate into myofibroblasts and deposit collagen in the infarct area. This is mediated by a variety of growth factors, including components of a local reninangiotensin-aldosterone system. In the final phase, the newly formed scar is consolidated through cross-linking of collagen fibers and other extracellular matrix components. The extracellular matrix plays an important role in the healing process, and an imbalance between matrix deposition and degradation can lead to adverse myocardial remodeling spiraling to heart failure. Excessive collagen deposition beyond the infarct area contributes to myocardial stiffening and loss of contractile function. On the other hand, inadequate deposition of collagen or excessive collagen degradation can lead to infarct expansion, aneurysm formation, left ventricular (LV) dilation, and even cardiac rupture.MMP are a group of zinc-dependent enzymes that degrade a large variety of extracellular matrix proteins. Approximately 25 MMP have been described and classified in the functional subgroups gelatinases, collagenases, stromelysins, and membrane-type MMP. Extensive preclinical work has suggested detrimental effect of the gelatinases MMP-2 and MMP-9. Genetic knockout of MMP-9 1,2 and MMP-2 3 restricted inflammatory response and removal of necrotic tissue and collagen deposition after experimental MI; this was associated with reduction in LV dilation and incidence of of LV rupture. Moreover, knockout of endogenous tissue inhibitors of metalloproteinases (TIMP) resulted in increased hypertrophy, dilation, and cardiac dysfunction.4,5 Also, animal studies have shown that pharmacologic MMP inhibitors reduce remodeling.6,7 Therapeutic MMP inhibition has not been successfully translated to clinical efficacy.Targeting of cardiac MMP activity has been reported using optical imaging 8 and nuclear imaging [9][10][11] probes. A non-invasive SPECT imaging of MMP activity has been reported in experimental MI in mice employing Tc-99 m-labeled broad-spectrum MMP inhibitor RP805. 10 When comparing with control mice, uptake in infarct area was fivefold higher from week 1 to 3, with slight reduction over time. Interestingly, uptake was also twofold higher in remote area, suggesting that remote imaging could become feasible. In a follow-up study by the same group, the same probe was evaluated in a larger infarct model in porcine experiments.

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Molecular Imaging for Efficacy of Pharmacologic Intervention in Myocardial Remodeling

Cited by 62 publications

References 33 publications

Molecular Imaging of the Cardiac Extracellular Matrix

Molecular Imaging of the Cardiac Extracellular Matrix

A Randomized Study of the Beneficial Effects of Aldosterone Antagonism on LV Function, Structure, and Fibrosis Markers in Metabolic Syndrome

Playing slot to hitting the jackpot in molecular imaging: On probability of uncovering subcellular pathogenesis vs achieving clinical applicability

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