Evolving role of molecular imaging for new understanding: targeting myofibroblasts to predict remodeling.

Containment of the process of cardiac remodeling is a prerequisite for prevention of development of heart failure (HF) after myocardial infarction. For personalization of therapeutic intervention strategy, it may be of benefit to identify the subset of patients who are at higher risk for development of HF. One such strategy may involve targeted imaging of various components involved in the remodeling process and interstitial fibrosis, including the myofibroblast.

Myocardial remodeling after infarction: the role of myofibroblasts.

Myofibroblasts have characteristics of fibroblasts and smooth muscle cells: they produce extracellular matrix and are able to contract. In so doing, they can contribute to tissue replacement and interstitial fibrosis following cardiac injury. The scar formed after myocardial injury is no longer considered to be passive tissue; it is an active playground where myofibroblasts play a role in collagen turnover and scar contraction.

Mouse strain determines the outcome of wound healing after myocardial infarction.

Aims: Our objective was to study the effect of the genetic background on the wound healing process after myocardial infarction (MI) in mice.

Methods And Results: MI was induced in five different mouse strains (BalbC, C57Bl6, FVB, 129S6, and Swiss). At 3, 14, and 28 days after MI, cardiac dimensions were monitored by echocardiography and histology, whereas cardiac function was determined by direct intraventricular pressure measurements (dP/dt).

Molecular imaging for efficacy of pharmacologic intervention in myocardial remodeling.

Objectives: Using molecular imaging techniques, we examined interstitial alterations during postmyocardial infarction (MI) remodeling and assessed the efficacy of antiangiotensin and antimineralocorticoid intervention, alone and in combination.

Background: The antagonists of the renin-angiotensin-aldosterone axis restrict myocardial fibrosis and cardiac remodeling after MI and contribute to improved survival. Radionuclide imaging with technetium-99m-labeled Cy5.

Macrophage depletion in hypertensive rats accelerates development of cardiomyopathy.

Inflammation contributes to the process of ventricular remodeling after acute myocardial injury. To investigate the role of macrophages in the chronic process of cardiac remodeling, they were selectively depleted by intravenous administration of liposomal clodronate in heart failure-prone hypertensive Ren-2 rats from the age of 7 until 13 weeks. Plain liposomes were used for comparison.

Molecular imaging of interstitial alterations in remodeling myocardium after myocardial infarction.

Objectives: The purpose of this study was to evaluate interstitial alterations in myocardial remodeling using a radiolabeled Cy5.5-RGD imaging peptide (CRIP) that targets myofibroblasts.

Background: Collagen deposition and interstitial fibrosis contribute to cardiac remodeling and heart failure after myocardial infarction (MI).

Defective intercellular adhesion complex in myocardium predisposes to infarct rupture in humans.

Objectives: Our goal was to evaluate intercellular adhesion complex proteins in myocardium in human infarct rupture.

Background: Infarct rupture, a fatal complication of myocardial infarction (MI), has been attributed to a defective cell adhesion complex in a transgenic mouse model.

Methods: Heart samples were collected from autopsies from infarct rupture and control (nonrupture) MI patients.

Increased matrix metalloproteinase-8 and -9 activity in patients with infarct rupture after myocardial infarction.

Background: Infarct rupture is a usually fatal complication of myocardial infarction (MI), for which no molecular mechanism has been described in humans. Experimental evidence in mouse models suggests that the degradation of the extracellular matrix by matrix metalloproteinases (MMPs) plays an important role in infarct rupture. The present study was designed to study the role of MMP-2, MMP-8, and MMP-9 in human infarct rupture.

Transglutaminase activity in acute infarcts predicts healing outcome and left ventricular remodelling: implications for FXIII therapy and antithrombin use in myocardial infarction.

Aims: The transglutaminase factor XIII (FXIII) emerges as a key enzyme in healing after myocardial infarction (MI). Here we assess the impact of transglutaminase-modulating therapies on healing and evolution of heart failure using a novel, non-invasive molecular imaging technique.

Methods And Results: Immunoblotting revealed lower FXIII levels in the myocardium of nine patients with infarct rupture when compared to MI patients without rupture (P < 0.

Interruption of Wnt signaling attenuates the onset of pressure overload-induced cardiac hypertrophy.

The hypertrophic response of the heart has been recognized recently as the net result of activation of prohypertrophic and antihypertrophic pathways. Here we report the involvement of the Wnt/Frizzled pathway in the onset of cardiac hypertrophy development. Stimulation of the Wnt/Frizzled pathway activates the disheveled (Dvl) protein.