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Results for “Integrin alphaVbeta3”

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PubMed2005

Design and synthesis of novel platelet fibrinogen receptor antagonists with 2H-1,4-benzoxazine-3(4H)-one scaffold. A systematic study.

New platelet glycoprotein IIb/IIIa (GP IIb/IIIa, integrin alpha(IIb)beta3) antagonists were prepared on a 2H-1,4-benzoxazine-3(4H)-one scaffold. Their anti-aggregatory activities in human platelet rich plasma and their affinity towards alpha(IIb)beta3 and alpha(V)beta3 integrins were assessed. Various substitution positions and side chain variations were studied. In contrast to the generally accepted model, compounds containing ethyl esters as aspartate mimetics were in general more active than the corresponding free acids. We suggest an explanation for the observed behaviour of these new compounds.

Aspartic Acid↗

PubMed2005

Difference in alpha(v)beta3 integrin expression in endometrial stromal cell in subgroups of women with unexplained infertility.

OBJECTIVE: The aim of the study was to evaluate the endometrial receptivity by using alpha(v)beta3 expression in the midsecretory phase in different endometrial compartments in women with unexplained infertility. STUDY DESIGN: A prospective controlled clinical trial in a setting of a university teaching hospital was performed. Thirty-three fertile and 33 infertile women were included in the study. Midluteal endometrial biopsies of the endometrium were carried out during the implantation window. Immunohistochemical staining was performed for the expression of alpha(v)beta3 in endometrial samples. Alpha(v)beta3 expression was measured using the HSCORE scoring system in the endometrial glandular and luminal epithelium and in the endometrial stroma. Serum levels of estradiol, progesterone, follicle-stimulating hormone, luteinizing hormone, thyroid-stimulating hormone, prolactin, total testosterone and dehydroepiandrosterone sulphate were measured in the early follicular phase and in the midluteal phase. RESULTS: The average alpha(v)beta3 integrin expression at different sites of the endometrium was not different in the infertile and fertile controls. However, the stromal alpha(v)beta3 integrin was found to be expressed significantly less in a subgroup of women with lower than average alpha(v)beta3 integrin expression in luminal epithelium than in fertile controls and significantly more in a subgroup of women with higher than average alpha(v)beta3 integrin expression in luminal epithelium. There was no difference in stromal alpha(v)beta3 integrin expression in the lower or higher glandular alpha(v)beta3 integrin expression subgroups. CONCLUSIONS: Alpha(v)beta3 integrin expression in endometrial stromal cells may be different in subgroups of women with unexplained infertility.

Adult↗

PubMed2005

The effect of the antibody used and method of quantification on oral mucosal vascularity.

A vast literature exists on angiogenesis particularly with regard to understanding tumour growth and development. This is no less true for oral cancer, where slight variations in protocols may invalidate comparison between studies. The influence of tissue processing, and the specific antibody and method of quantification used to identify blood vessels was assessed with respect to oral mucosal vascularity. The angiogenic profile of 20 frozen sections of clinically normal oral mucosa were compared with 16 paraffin-embedded specimens. Eight of the frozen specimens had matched paraffin-embedded tissue. Vascular antigens were identified immunohistochemically using four antibodies and blood vessel density was measured by three methods. CD31 and von Willebrand's factor (vWF) counts were higher than alpha-smooth muscle actin and alphanubeta3. Results for CD31 were higher in frozen tissue than paraffin-embedded tissue. Significantly more CD31-positive vessels were found in frozen tissue in the cohort of matched samples. For paraffin-embedded tissue vWF gave higher values for vascularity than CD31. The variation in antibody reaction to these markers of blood vessels suggests that the antibody employed and method of fixation is more important than the method of quantification used. Comparison of the results for fresh frozen tissue and paraffin-processed tissue suggests that this is acceptable for vWF but not for CD31.

Actins↗

PubMed2006

Integrin alpha v beta 3 antagonist Cilengitide enhances efficacy of radiotherapy in endothelial cell and non-small-cell lung cancer models.

PURPOSE: Integrins alpha v beta 3 and alpha v beta 5 are important in tumor growth and angiogenesis and have been recently explored as targets for cancer therapy. Radiotherapy also inhibits tumor growth and affects vasculature. We explored the combination of integrin antagonist Cilengitide (EMD 121974) and ionizing radiation. METHODS AND MATERIALS: Levels of alpha v beta 3 were determined for human umbilical vein endothelial cells (HUVEC), as well as H157 and H460 human non-small-cell lung cancer cells, using FACS analysis and immunofluorescence imaging. Clonogenic assays, Western immunoblots probed for cleaved caspase 3, and Annexin-V probing were used to evaluate cell survival and apoptosis. A cell detachment assay and matrigel assay were used to further examine the effects of treatment. RESULTS: Human umbilical vein endothelial cells had the highest alpha v beta 3 level, followed by H157, and H460. Interestingly, we found that 5 Gy irradiation induced expression of alpha v beta 3 in all cell lines. Clonogenic assays showed a radiosensitizing effect with Cilengitide, and calculation of the dose enhancement ratio showed that the effect was highest in HUVECs (1.38), followed by H157 (1.19), and H460 (1.10), corresponding to the levels of target expression. There was an increase in apoptotic cells after combination treatment with Cilengitide and radiation, and there was an increase in detached cells after treatment with Cilengitide. Additionally, there was decreased endothelial tubule formation after combination treatment. CONCLUSIONS: We conclude that radiation induces expression of alpha v beta 3 integrin in endothelial and non-small-cell lung cancer models, and that integrin antagonist Cilengitide is a radiosensitizer in proportion to the levels of target integrin expression.

Apoptosis↗

PubMed2006

Noninvasive characterization of myocardial molecular interventions by integrated positron emission tomography and computed tomography.

OBJECTIVES: We sought to investigate the usefulness of integrated positron emission tomography (PET) and computed tomography (CT) for in vivo characterization of an angiogenesis-directed molecular intervention. BACKGROUND: Controversies about the effectiveness of molecular therapies for cardiovascular disease have prompted the need for more powerful noninvasive imaging techniques. METHODS: In a model of regional adenoviral transfer of the VEGF(121) gene to myocardium of healthy pigs, PET-CT using multiple molecular-directed radiotracers was employed. RESULTS: Two days after gene transfer, successful transgene expression was noninvasively confirmed by a reporter probe targeting co-expressed HSV1-sr39tk reporter gene. The CT-derived ventricular function and morphology remained unaltered (left ventricular ejection fraction 57 +/- 5% in adenovirus-injected animals vs. 53 +/- 5% in controls; p = 0.36). Increased regional perfusion was identified in areas overexpressing VEGF (myocardial blood flow during adenosine-induced vasodilation 1.47 +/- 0.49 vs. 1.14 +/- 0.27 ml/g/min in remote areas; p = 0.01), corroborating in vivo effects on microvascular tone and permeability. Finally, regional angiogenesis-associated alpha(v)beta3 integrin expression was not enhanced, suggesting little contribution to the perfusion increase. Fusion of CT morphology and tracer-derived molecular signals allowed for accurate regional localization of biologic signals. Findings were validated by control vectors, sham-operated animals, and ex vivo tissue analysis. CONCLUSIONS: Integrated PET-CT has the potential to dissect cardiovascular biologic mechanisms from gene expression to physiologic function and morphology. The VEGF overexpression in healthy myocardium increases myocardial perfusion without significant up-regulation of alpha(v)beta3 integrin adhesion molecules early after the intervention.

Animals↗

PubMed2004

High-throughput sample preparation procedures for the quantitation of a new bone integrin alpha(nu)beta(3) antagonist in human plasma and urine using liquid chromatography-tandem mass spectrometry.

High throughput LC-MS/MS assays to quantitate a new alpha(nu)beta(3) bone integrin antagonist (I) in human plasma and urine have been developed using instruments programmed to automate sample preparation procedures. Packard liquid handling system-MultiPROBE II EX was programmed for preparing calibration standards in control plasma and urine, acidifying all standards, quality control (QC), and clinical samples with necessary dilutions, and adding the internal standard to the acidified samples. TOMTEC Quadra 96 was programmed to perform the solid phase extraction (SPE) process on a 3M 96-well mixed phase cation standard density (MPC-SD) plate to isolate the analytes from the sample matrix. The extract collected from both types of matrices was directly injected into reversed-phase LC-MS/MS system with a Turbo Ion Spray (TIS) interface in the positive ionization mode. The plasma and urine assays have the calibration range of 0.5-1500 and 2-6000 ng/mL, respectively. Validation of the automated and the manual plasma assays showed that application of MultiPROBE II to sample preparation gave comparable accuracy and precision. Overall, the automated approaches with minimum manual intervention enhanced the throughput of sample preparation.

Bone and Bones↗

PubMed2003

Modulation of secretory functions in epithelia by adenovirus capsid proteins.

To evaluate the safety of adenovirus-derived capsid proteins for ocular gene delivery, we have investigated their effects on the morphology and function of the acinar epithelial cells of the lacrimal gland. These cells are responsible for basal and stimulated release of proteins and electrolytes into ocular fluid, a process essential in maintaining the health of the ocular surface. Acinar epithelial cells from rabbit lacrimal gland were exposed to one of two adenovirus serotype 5 capsid proteins, penton or knob (the carboxy-terminal fragment of the fiber capsid protein). Sustained (16-18 h) exposure to the penton at 20 microg/ml was associated with major changes in the organization of the regulated secretory pathway and cytoskeleton. These changes included an apparent loss of mature secretory vesicles enriched in rab3D around the apical lumen as well as a depletion of apical actin. The microtubule array in penton-treated acini also exhibited bundling and disorganization. None of these effects were elicited by exposure to knob protein. Penton treatment also caused a significant (p < or = 0.05) increase and decrease in basal and carbachol-stimulated release, respectively, of bulk protein. Competition studies showed that RGD peptide partially prevented the penton-induced changes in rab3D-enriched secretory vesicles and actin filaments. These findings suggest that the adenovirus penton protein compromises normal acinar secretory compartment organization and function and that these changes are due at least partly to penton-integrin interactions.

Actins↗

PubMed2004

Self-assembled nanoparticles based on glycol chitosan bearing 5beta-cholanic acid for RGD peptide delivery.

The synthetic peptide bearing Arg-Gly-Asp (RGD) sequence is considered to specifically bind to alpha(v)beta(3) integrin expressed on endothelial cells in the angiogenic blood vessels, which provides a potential to inhibit the tumor growth. As a carrier for the RGD peptide, hydrophobically modified glycol chitosan (HGC) capable of forming nano-sized self-aggregates was prepared by the chemical conjugation of 5beta-cholanic acid to the main backbone of glycol chitosan. The RGD peptide labeled with fluoresein isothiocyanate (FITC-GRGDS) was loaded into self-aggregates in three different conditions: simple mixing, sonication, and solvent evaporation methods. Of different methods applied, solvent evaporation method showed the most promising results for peptide loading, as judged by the yield (>70%) and loading efficiency (>75%). It was found that the presence of FITC-labeled peptides makes the self-aggregates to be compact, possibly due to the role of both hydrophobic FITC and peptides containing carboxylic acids that allow hydrogen bonding and electrostatic interaction with the primary amino groups in the main backbone of glycol chitosan. FITC-labeled peptides were released from self-aggregates in a physiological solution (pH 7.4) for up to 1 day. From the cell adhesion and migration assays, it was demonstrated that FITC labeling of peptides does not significantly deteriorate biological activity of the parent peptide drug (GRGDS). Overall, the self-aggregates loaded with FITC-GRGDS might be useful for monitoring or destroying the angiogenic vessels surrounding the tumor tissue.

Amino Acid Sequence↗

PubMed2006

The role of osteopontin in tendon tissue remodeling after denervation-induced mechanical stress deprivation.

It has been shown that musculoskeletal tissues undergo dynamic tissue remodeling by a process that is quite sensitive to the mechanical environment. However, the detailed molecular mechanism underlying this process remains unclear. We demonstrate here that after denervation-induced mechanical stress deprivation, tendons undergo dynamic tissue remodeling as evidenced by a significant reduction of the collagen fibril diameter. Importantly, the transient up-regulation of osteopontin (OPN) expression was characteristic during the early phase of tendon tissue remodeling. Following this dynamic change of OPN expression, matrix metalloproteinase (MMP)-13 expression was induced, which presumably accounts for the morphological changes of tendon by degrading tendon collagen fibrils. The modulation of MMP-13 expression by OPN was specific, since the expression of MMP-2, which is also known to be involved in tissue remodeling, did not alter in the tendons under the absence or presence of OPN. We also demonstrate that the modulation of MMP-13 expression by OPN is due to the signaling through cell surface receptors for OPN. Thus, we conclude that OPN plays a crucial role in conveying the effect of denervation-induced mechanical stress deprivation to the tendon fibroblasts to degrade the extracellular matrices by regulating MMP-13 expression in tendon fibroblasts.

Animals↗

PubMed2004

18F-labeled RGD peptide: initial evaluation for imaging brain tumor angiogenesis.

Brain tumors are highly angiogenesis dependent. The cell adhesion receptor integrin alpha(v)beta(3) is overexpressed in glioma and activated endothelial cells and plays an important role in brain tumor growth, spread and angiogenesis. Suitably labeled alpha(v)beta(3)-integrin antagonists may therefore be useful for imaging brain tumor associated angiogenesis. Cyclic RGD peptide c(RGDyK) was labeled with (18)F via N-succinimidyl-4-[(18)F]fluorobenzoate through the side-chain epsilon-amino group of the lysine residue. The radiotracer was evaluated in vivo for its tumor targeting efficacy and pharmacokinetics in subcutaneously implanted U87MG and orthotopically implanted U251T glioblastoma nude mouse models by means of microPET, quantitative autoradiography and direct tissue sampling. The N-4-[(18)F]fluorobenzoyl-RGD ([(18)F]FB-RGD) was produced in less than 2 h with 20-25% decay-corrected yields and specific activity of 230 GBq/micromol at end of synthesis. The tracer showed very rapid blood clearance and both hepatobiliary and renal excretion. Tumor-to-muscle uptake ratio at 30 min was approximately 5 in the subcutaneous U87MG tumor model. MicroPET imaging with the orthotopic U251T brain tumor model revealed very high tumor-to-brain ratio, with virtually no uptake in the normal brain. Successful blocking of tumor uptake of [(18)F]FB-RGD in the presence of excess amount of c(RGDyK) revealed receptor specific activity accumulation. Hence, N-4-[(18)F]fluorobenzoyl labeled cyclic RGD peptide [(18)F]FB-RGD is a potential tracer for imaging alpha(v)beta(3)-integrin positive tumors in brain and other anatomic locations.

Animals↗

PubMed2006

An improved method of 18F peptide labeling: hydrazone formation with HYNIC-conjugated c(RGDyK).

Radiolabeled alpha(v)beta(3)-integrin antagonists are increasingly investigated as a means of imaging angiogenesis. Several methods of labeling alpha(v)beta(3)-integrin binding peptide with (18)F have been reported recently. In the present study, we devised a straightforward means for labeling Arg-Gly-Asp (RGD) peptide with (18)F via hydrazone formation between c(RGDyK)-hydrazinonicotinic acid (HYNIC) (3) and 4-[(18)F]-fluorobenzaldehyde ([(18)F]4). The resulting reaction mixture was purified by HPLC to give 4'-[(18)F]-fluorobenzylidenehydrazone-6-nicotinamide-c(RGDyK) ([(18)F]5). The conjugation efficiency of 3 and 4 to form [(18)F]5 was 95.2%, and the radiochemical purity of [(18)F]5 after purification was >99%. The specific activity of [(18)F]5 estimated by radio-HPLC was 20.5 GBq/mumol (end of synthesis). Competitive binding assay of c(RGDyK) (1) and 5 was performed using [(125)I]iodo-c(RGDyK) as a radioligand, and K(i) values were found to be 2.8 and 21.7 nM, respectively. For the biodistribution study, the angiogenic mouse model was established by inducing unilateral ischemia on the left hindlimbs of ICR mice after femoral artery ablation. Seven days after inducing ischemia, [(18)F]5 was administered to the mice through the tail vein. Ischemic muscle uptake of [(18)F]5 was significantly higher than that of normal muscle (P<.01). Specific uptake was confirmed by coinjection of 1 with [(18)F]5. Here, we successfully labeled RGD peptide with (18)F via hydrazone formation between 3 and 4, resulting to [(18)F]5. [(18)F]5 was found to have high affinity for alpha(v)beta(3)-integrin and to accumulate specifically in ischemic hindlimb muscle of mice. We suggest that (18)F labeling via formation of hydrazone between HYNIC peptide and [(18)F]4 is a useful method for labeling c(RGDyK), which can be applied for imaging angiogenesis.

Animals↗

PubMed2007

Effects of linker variation on the in vitro and in vivo characteristics of an 111In-labeled RGD peptide.

INTRODUCTION: Due to the selective expression of the alpha(v)beta3 integrin in tumors, radiolabeled arginine-glycine-aspartic acid (RGD) peptides are attractive candidates for tumor targeting. Minor modifications of these peptides could have a major impact on in vivo characteristics. In this study, we systematically investigated the effects of linker modification between two cyclic RGD sequences and DOTA (1,4,7,10-tetraazadodecane-N,N',N",N'''-tetraacetic acid) on the in vitro and in vivo characteristics of the tracer. METHODS: A dimeric RGD peptide was synthesized and conjugated either directly with DOTA or via different linkers: PEG4 (polyethylene glycol), glutamic acid or lysine. The RGD peptides were radiolabeled with 111In, and their in vitro and in vivo alpha(v)beta3-binding characteristics were determined. RESULTS: LogP values varied between -2.82+/-0.06 and -3.95+/-0.33. The IC50 values for DOTA-E-[c(RGDfK)]2, DOTA-PEG4-E-[c(RGDfK)]2, DOTA-E-E-[c(RGDfK)]2 and DOTA-K-E-[c(RGDfK)]2 were comparable. Two hours after injection, the tumor uptakes of the 111In-labeled compounds were not significantly different. The kidney accumulation of [111In]-DOTA-K-E-[c(RGDfK)]2 [4.05+/-0.20% of the injected dose per gram (ID/g)] was significantly higher as compared with that of [111In]-DOTA-E-[c(RGDfK)]2 (2.63+/-0.19% ID/g; P<.05) as well as that of [111In]-DOTA-E-E-[c(RGDfK)]2 (2.16+/-0.21% ID/g; P<.01). The liver uptake of [111In]-DOTA-E-E-[c(RGDfK)]2 (2.12+/-0.09% ID/g) was significantly higher as compared with that of [111In]-DOTA-E-[c(RGDfK)]2 (1.64+/-0.1% ID/g; P<.05) as well as that of [111In]-DOTA-K-E-[c(RGDfK)]2 (1.52+/-0.04% ID/g; P<.01). CONCLUSIONS: Linker variation did not affect affinity for alpha(v)beta3 and tumor uptake. Insertion of lysine caused enhanced kidney retention; that of glutamic acid also resulted in enhanced retention in the kidneys. PEG4 appeared to be the most suitable linker as compared with glutamic acid and lysine because it has the highest tumor-to-blood ratio and the lowest uptake in the kidney and liver.

Animals↗

PubMed2005

Expression, purification, and characterization of a neovasculature targeted rmhTNF-alpha in Escherichia coli.

The tumor vasculature is a suitable target for cancer treatment. RGD-4C (CDCRGDCFC) peptide can bind to human alphav integrins, which are known to be selectively expressed in human tumor blood vessels. Some studies showed that coupling anticancer drugs or peptides to the RGD peptides yielded compounds with increased efficacy against tumors and lowered toxicity to normal tissues in mice. TNF-alpha mutant (rmhTNF-alpha) that we previously constructed has been proved to have stronger antitumor effect compared with TNF-alpha. To increase antitumor effect and lower toxicity of rmhTNF-alpha, we coupled RGD4C to the N-terminal of rmhTNF-alpha (termed RGD4C-rmhTNF) and expressed RGD4C-rmhTNF in Escherichia coli. Here, we describe the expression, purification, and characterization of RGD4C-rmhTNF.

Animals↗

PubMed2004

Structural insights into how the MIDAS ion stabilizes integrin binding to an RGD peptide under force.

Integrin alpha(V)beta(3) binds to extracellular matrix proteins through the tripeptide Arg-Gly-Asp (RGD), forming a shallow crevice rather than a deep binding pocket. A dynamic picture of how the RGD-alpha(V)beta(3) complex resists dissociation by mechanical force is derived here from steered molecular dynamic (SMD) simulations in which the major force peak correlates with the breaking of the contact between Asp(RGD) and the MIDAS ion. SMD predicts that the RGD-alpha(V)beta(3) complex is stabilized from dissociation by a single water molecule tightly coordinated to the divalent MIDAS ion, thereby blocking access of free water molecules to the most critical force-bearing interaction. The MIDAS motif is common to many other proteins that contain the phylogenetically ancient von Willebrand A (vWA) domain. The functional role of single water molecules tightly coordinated to the MIDAS ion might reflect a general strategy for the stabilization of protein-protein adhesion against cell-derived forces through divalent cations.

Binding Sites↗

PubMed2005

Recombinant adenovirus type 5 vectors that target DC-SIGN, ChemR23 and alpha(v)beta3 integrin efficiently transduce human dendritic cells and enhance presentation of vectored antigens.

Recombinant adenoviruses (rAds) represent a promising system for vaccine delivery but transduce dendritic cells (DC) relatively poorly. To address this concern, we used a biotin-avidin linkage to conjugate rAd vectors to ligands which bind with high affinity to selected receptors on DC (ChemR23, alpha(v)beta3 integrin, and DC-SIGN). The targeted vectors had an enhanced ability to transduce human monocyte-derived DC compared to untargeted virus. In addition, DC transduced with targeted rAd vectors were more efficient at stimulating cytokine production by autologous memory CD8+ T cells, against a vector-encoded antigen. These results expand the range of cell surface receptors that can be used to target rAd5 vectors to DC, and may facilitate future development of rAd-based vaccines.

Adenoviridae↗

PubMed2004

Bovine aortic endothelial cells are susceptible to Hantaan virus infection.

Hantavirus serotype Hantaan (HTN) is one of the causative agents of hemorrhagic fever with renal syndrome (HFRS, lethality up to 10%). The natural host of HTN is Apodemus agrarius. Recent studies have shown that domestic animals like cattle are sporadically seropositive for hantaviruses. In the present study, the susceptibility of bovine aortic endothelial cells (BAEC) expressing alpha(V)beta(3)-integrin to a HTN infection was investigated. Viral nucleocapsid protein and genomic RNA segments were detected in infected BAEC by indirect immunofluorescence assay, Western blot analysis, and reverse transcription-polymerase chain reaction (RT-PCR), respectively. The results of this study strongly support our previous observation on Puumala virus (PUU) that has been propagated efficiently in BAEC. These findings open a new window to contemplate the ecology of hantavirus infection and transmission route from animal to man.

Animals↗

PubMed2006

Evidence for a differential functional regulation of the two beta(3)-integrins alpha(V)beta(3) and alpha(IIb)beta(3).

The functional regulation of integrins is a major determinant of cell adhesion, migration and tissue maintenance. The binding of cytoskeletal proteins to various sites of integrin cytoplasmic domains is a key mechanism of this functional regulation. Expression of recombinant integrin alpha(IIb)beta(3) and alpha(M)beta(2) lacking the GFFKR-region in CHO cells results in constitutively activated integrins. In contrast, CHO cells stably expressing either a GFFKR-deleted alpha(V(del))beta(3) or a FF to AA-substituted alpha(V(AA))beta(3) do not reveal a constitutively activated integrin. Adhesion to immobilized fibrinogen is strongly impaired in alpha(V(del))beta(3) or alpha(V(AA))beta(3)-expressing cells, whereas it is not impaired in alpha(IIb)beta(3) and alpha(M)beta(2), both lacking the GFFKR-region. In a parallel plate flow chamber assay, alpha(V)beta(3)-expressing cells adhere firmly to fibrinogen and spread even at shear rates of 15 to 20 dyn/cm(2), whereas alpha(V(del))beta(3) or alpha(V(AA))beta(3) cells are detached at 15 dyn/cm(2). Actin stress fiber formation and focal adhesion plaques containing alpha(V)beta(3) are observed in alpha(V)beta(3) cells but not in alpha(V(del))beta(3) or alpha(V(AA))beta(3)-expressing cells. As an additional manifestation of impaired outside-in signaling, phosphorylation of pp125(FAK) was reduced in these cells. In summary, we report that the GFFKR-region of the alpha(V)-cytoplasmic domain and in particular two phenylalanines are essential for integrin alpha(V)beta(3) function, especially for outside-in signaling. Our results suggest that the two beta(3)-integrins alpha(IIb)beta(3) and alpha(V)beta(3) are differentially regulated via their GFFKR-region.

Animals↗

PubMed2006

Molecular imaging of myocardial infarction.

Molecular tools are rapidly elucidating the molecular and cellular processes underlying myocardial infarction. To further understand these biological processes in vivo, investigators are embracing the burgeoning field of molecular imaging. Here we review important aspects of molecular imaging technology and then devote the majority of the text to studies that shed light on the in vivo pathogenesis of myocardial infarction. In particular, we focus on post-infarction healing and remodeling and discuss molecular imaging of proteolytic activity, angiogenesis, transglutaminase activity, and apoptosis. In the future, novel reporter agents and high-resolution cardiac imaging systems should enable imaging of emerging targets such as activated macrophages and myeloperoxidase activity, as well as stem cell-based and gene therapy-based myocardial regenerative strategies, in both experimental and clinical subjects.

Animals↗