scholarly journals [68Ga]Ga-NODAGA-E[(cRGDyK)]2 Angiogenesis PET/MR in a Porcine Model of Chronic Myocardial Infarction

Diagnostics ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1807
Author(s):  
Simon Bentsen ◽  
Andreas Clemmensen ◽  
Mathias Loft ◽  
Mette Flethøj ◽  
Karina Poulsdóttir Debes ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Integrin Αvβ3 ◽  
Scar Tissue ◽  
Tissue Formation ◽  
Ischemic Event ◽  
Healthy Myocardium ◽  
System A ◽  
In Vivo Detection ◽  
Infarct Border

Angiogenesis is crucial in tissue repair and prevents scar tissue formation following an ischemic event such as myocardial infarction. The ischemia induces formation of new capillaries, which have high expression of integrin αvβ3. [68Ga]Ga-NODAGA-E[(cRGDyK)]2 ([68Ga]Ga-RGD) is a promising PET-radiotracer reflecting angiogenesis by binding to integrin αvβ3. A Göttingen mini-pig underwent transient catheter-induced left anterior descending artery (LAD) occlusion for 120 min, and after 8 weeks was imaged on a Siemens mMR 3T PET/MR system. A large antero-septal infarction was evident by late gadolinium enhancement (LGE) on the short axis and 2–4 chamber views. The infarcted area corresponded to the area with high [68Ga]Ga-RGD uptake on the fused PET/MR images, with no uptake in the healthy myocardium. To support the hypothesis that [68Ga]Ga-RGD uptake reflects angiogenesis, biopsies were sampled from the infarct border and healthy myocardium. Expression of αvβ3 was evaluated using immunohistochemistry. The staining showed higher αvβ3 expression in the capillaries of the infarct border compared to those in the healthy myocardium. These initial data confirm in vivo detection of angiogenesis using [68Ga]Ga-RGD PET in a translational model, which overall support the method applicability when evaluating novel cardio-protective therapies.

scholarly journals Novel Identified Circular Transcript of RCAN2, circ-RCAN2, Shows Deviated Expression Pattern in Pig Reperfused Infarcted Myocardium and Hypoxic Porcine Cardiac Progenitor Cells In Vitro

2021 ◽  
Vol 22 (3) ◽  
pp. 1390
Author(s):  
Julia Mester-Tonczar ◽  
Patrick Einzinger ◽  
Johannes Winkler ◽  
Nina Kastner ◽  
Andreas Spannbauer ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Progenitor Cells ◽  
Regulatory Networks ◽  
Circular Rnas ◽  
Cardiac Progenitor Cells ◽  
Tissue Samples ◽  
Healthy Myocardium ◽  
Acute Mi

Circular RNAs (circRNAs) are crucial in gene regulatory networks and disease development, yet circRNA expression in myocardial infarction (MI) is poorly understood. Here, we harvested myocardium samples from domestic pigs 3 days after closed-chest reperfused MI or sham surgery. Cardiac circRNAs were identified by RNA-sequencing of rRNA-depleted RNA from infarcted and healthy myocardium tissue samples. Bioinformatics analysis was performed using the CIRIfull and KNIFE algorithms, and circRNAs identified with both algorithms were subjected to differential expression (DE) analysis and validation by qPCR. Circ-RCAN2 and circ-C12orf29 expressions were significantly downregulated in infarcted tissue compared to healthy pig heart. Sanger sequencing was performed to identify the backsplice junctions of circular transcripts. Finally, we compared the expressions of circ-C12orf29 and circ-RCAN2 between porcine cardiac progenitor cells (pCPCs) that were incubated in a hypoxia chamber for different time periods versus normoxic pCPCs. Circ-C12orf29 did not show significant DE in vitro, whereas circ-RCAN2 exhibited significant ischemia-time-dependent upregulation in hypoxic pCPCs. Overall, our results revealed novel cardiac circRNAs with DE patterns in pCPCs, and in infarcted and healthy myocardium. Circ-RCAN2 exhibited differential regulation by myocardial infarction in vivo and by hypoxia in vitro. These results will improve our understanding of circRNA regulation during acute MI.

Layer-specific strain analysis: investigation of regional deformations in a rat model of acute versus chronic myocardial infarction

2012 ◽  
Vol 303 (5) ◽  
pp. H549-H558 ◽  
Author(s):  
Noa Bachner-Hinenzon ◽  
Offir Ertracht ◽  
Assaf Malka ◽  
Marina Leitman ◽  
Zvi Vered ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Wall Thickness ◽  
Strain Analysis ◽  
Scar Tissue ◽  
The Other ◽  
Tissue Formation ◽  
Operating Characteristics ◽  
Specific Strain ◽  
Characteristics Analysis ◽  
Extent Of Damage

Myocardial infarction (MI) injury extends from the endocardium toward the epicardium. This phenomenon should be taken into consideration in the detection of MI. To study the extent of damage at different stages of MI, we hypothesized that measurement of layer-specific strain will allow better delineation of the MI extent than total wall thickness strain at acute stages but not at chronic stages, when fibrosis and remodeling have already occurred. After baseline echocardiography scans had been obtained, 24 rats underwent occlusion of the left anterior descending coronary artery for 30 min followed by reperfusion. Thirteen rats were rescanned at 24 h post-MI and eleven rats at 2 wk post-MI. Next, rats were euthanized, and histological analysis for MI size was performed. Echocardiographic scans were postprocessed by a layer-specific speckle tracking program to measure the peak circumferential strain (SCpeak) at the endocardium, midlayer, and epicardium as well as total wall thickness SCpeak. Linear regression for MI size versus SCpeak showed that the slope was steeper for the endocardium compared with the other layers ( P < 0.001), meaning that the endocardium was more sensitive to MI size than the other layers. Moreover, receiver operating characteristics analysis yielded better sensitivity and specificity in the detection of MI using endocardial SCpeak instead of total wall thickness SCpeak at 24 h post-MI ( P < 0.05) but not 2 wk later. In conclusion, at acute stages of MI, before collagen deposition, scar tissue formation, and remodeling have occurred, damage may be nontransmural, and thus the use of endocardial SCpeak is advantageous over total wall thickness SCpeak.

scholarly journals Direct Cardiac Reprogramming: Advances in Cardiac Regeneration

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Olivia Chen ◽  
Li Qian
Keyword(s):  
Myocardial Infarction ◽  
Heart Disease ◽  
Cell Fate ◽  
Early Stage ◽  
Cardiac Injury ◽  
Cardiac Regeneration ◽  
Scar Tissue ◽  
Coronary Events

Heart disease is one of the lead causes of death worldwide. Many forms of heart disease, including myocardial infarction and pressure-loading cardiomyopathies, result in irreversible cardiomyocyte death. Activated fibroblasts respond to cardiac injury by forming scar tissue, but ultimately this response fails to restore cardiac function. Unfortunately, the human heart has little regenerative ability and long-term outcomes following acute coronary events often include chronic and end-stage heart failure. Building upon years of research aimed at restoring functional cardiomyocytes, recent advances have been made in the direct reprogramming of fibroblasts toward a cardiomyocyte cell fate bothin vitroandin vivo. Several experiments show functional improvements in mouse models of myocardial infarction followingin situgeneration of cardiomyocyte-like cells from endogenous fibroblasts. Though many of these studies are in an early stage, this nascent technology holds promise for future applications in regenerative medicine. In this review, we discuss the history, progress, methods, challenges, and future directions of direct cardiac reprogramming.

scholarly journals Tendon Cell Deletion of IKKβ/NF-κB Drives Functionally Deficient Tendon Healing and Altered Cell Survival Signaling In Vivo

2020 ◽  
Author(s):  
Katherine T. Best ◽  
Emma Knapp ◽  
Constantinos Ketonis ◽  
Jennifer H. Jonason ◽  
Hani A. Awad ◽  
...  
Keyword(s):  
Cell Survival ◽  
Flexor Tendon ◽  
Tendon Repair ◽  
Tendon Healing ◽  
Scar Tissue ◽  
Cell Populations ◽  
Tissue Formation ◽  
Matrix Deposition ◽  
Scar Tissue Formation

AbstractAcute tendon injuries are characterized by excessive matrix deposition that impedes regeneration and disrupts functional improvements. Inflammation is postulated to drive pathologic scar tissue formation, with nuclear factor kappa B (NF-κB) signaling emerging as a candidate pathway in this process. However, characterization of the spatial and temporal activation of canonical NF-κB signaling during tendon healing in vivo, including identification of the cell populations activating NF-κB, is currently unexplored. Therefore, we aimed to determine which cell populations activate canonical NF-κB signaling following flexor tendon repair with the goal of delineating cell-specific functions of NF-κB signaling during scar mediated tendon healing. Immunofluorescence revealed that both tendon cells and myofibroblasts exhibit prolonged activation of canonical NF-κB signaling into the remodeling phase of healing. Using cre-mediated knockout of the canonical NF-κB kinase (IKKβ), we discovered that suppression of canonical NF-κB signaling in Scleraxis-lineage cells increased myofibroblast content and scar tissue formation. Interestingly, Scleraxis-lineage specific knockout of IKKβ increased the incidence of apoptosis, suggesting that canonical NF-κB signaling may be mediating cell survival during tendon healing. These findings suggest indispensable roles for canonical NF-κB signaling during flexor tendon healing.One Sentence SummaryScleraxis-lineage specific knockdown of persistent canonical IKKβ/NF-κB drives scar formation and apoptotic signaling during flexor tendon healing.

Abstract 1096: Cytokine Enhancement with Hgf Or Vegf in the Infarct Border Zone is Key to Attenuating the Negative Remodelling after Myocardial Infarction

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Sonja Schrepfer ◽  
Tobias Deuse ◽  
Christoph Peter ◽  
William Stein ◽  
Tim Doyle ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Treatment Strategies ◽  
Border Zone ◽  
Cytokine Release ◽  
Intramyocardial Injection ◽  
Paracrine Effects ◽  
Infarct Border Zone ◽  
Infarct Border

Adult mesenchymal stem cell (MSC)-based treatment strategies have been proposed to alleviate the consequences of myocardial infarction (MI). The cytokine release of ischemic myocardium was investigated in vivo after LAD ligations in mice and in vitro in cultured cardiomyocytes. Of all cytokines that were at least 5-fold upregulated during ischemia, only HGF and VEGF proved to promote MSC proliferation, and chemotaxis in vitro. Homing of intranenously (IV) injected MSCs (0.5×106 per animal) into the infarct border zone after LAD ligation was inefficient (1±0.5 cells/HPF). Cytokine enhancement (CE) of HGF or VEGF by intramyocardial injection at the time of MI significantly facilitated MSC homing (11±4 cells/HPF and 7±4 cells/HPF, respectively; p=0.001). To our knowledge, this is the first study monitoring cardiac geometry and function over a long-term period of 6 months. using ECG-triggered contrast Micro-CT. It revealed that the progressive decrease in EF over time (to 19±1%) could be attenuated by CE with HGF (29±6%; p=0.003) or VEGF (28±4%; p=0.004) and subsequent IV MSC injection. However, LVEFs of animals treated with CE with HGF or VEGF only, but received no MSC injection, were similar to those groups that also received IV MSCs (p=0.127 and p=0.54, respectively). Best results were finally achieved by prolonged presence of HGF or VEGF, achieved by intramyocardial injection of MSCs stably transfected to produce HGF or VEGF and firefly luciferase into the infarct border zone. Duration of cytokine release was estimated by monitoring MSC survival using in vivo bioluminescence imaging (BLI). BLI signals were detectable for 10 days in contrast to the rapid fate of the cytokines after single dose administration in the CE group, resulting in preserved LVEFs at 6 months This study highlights the beneficial effect of HGF and VEGF to attenuate the negative LV remodelling after MI and diminishes the role of the MSCs to a pure delivery system for paracrine effects.

Canine Acute Myocardial Infarction In Vivo Detection by MRI with Gradient Echo Technique and Contribution of Gd-DOTA

1988 ◽  
Vol 23 (1) ◽  
pp. S258 ◽  
Author(s):  
ELISABETH SCHOUMAN-CLAEYS ◽  
GUY FRIJA ◽  
DIDIER REVEL ◽  
DIDIER DOUCET ◽  
ANNE-MARIE DONADIEU
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Gradient Echo ◽  
In Vivo Detection

Canine Acute Myocardial Infarction In Vivo Detection by MRI with Gradient Echo Technique and Contribution of Gd-DOTA

1988 ◽  
Vol 23 ◽  
pp. S254-S257 ◽  
Author(s):  
ELISABETH SCHOUMAN-CLAEYS ◽  
GUY FRIJA ◽  
DIDIER REVEL ◽  
DIDIER DOUCET ◽  
ANNE-MARIE DONADIEU
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Gradient Echo ◽  
In Vivo Detection

Hemispherical photoacoustic imaging of myocardial infarction: in vivo detection and monitoring

2017 ◽  
Vol 28 (5) ◽  
pp. 2176-2183 ◽  
Author(s):  
Jing Lv ◽  
Ya Peng ◽  
Shi Li ◽  
Zhide Guo ◽  
Qingliang Zhao ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Photoacoustic Imaging ◽  
In Vivo Detection

Abstract 372: Regulation of Ski and Scleraxis in the Infarcted Rat Heart

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Krista L Filomeno ◽  
Sunil G Rattan ◽  
Sheri Bage ◽  
Matthew Zeglinski ◽  
Michael P Czubryt ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Wound Healing ◽  
Mrna Expression ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Scar Tissue ◽  
Sprague Dawley ◽  
Scar Area ◽  
Tgf Β1

Introduction: Coronary heart disease is causal to myocardial infarction (MI) and cardiac fibrosis. Upon ischemic myocardial injury, resident cardiac fibroblasts phenoconvert to myofibroblasts and synthesize large amounts of fibrillar collagens to produce scar tissue. Although the myofibroblast numbers are reduced in the infarct scar following the completion of wound healing, a sub-population of cells persist in the wounded area, leading to maladaptive chronic remodeling of the scar area and eventually the non-infarcted myocardium. Ski has been identified as a repressor of the TGF-β1 signaling pathway, attenuating the myofibroblast phenotype and its functional properties. Scleraxis has been implicated in canonical TGF-β1 signaling to promote collagen1α2 expression. We investigated how Ski and Scleraxis contribute to physiological and pathological wound healing in vivo. Methods: The study was carried out using 64 male Sprague-Dawley rats. The left anterior descending (LAD) coronary artery was ligated to induce a myocardial infarction. Control (sham) operated animals underwent surgery without ligation of the LAD artery. Animals were sacrificed at 2, 4, and 8 weeks post-MI and tissue collected for Western blot and qPCR studies. Results: Scleraxis mRNA expression remained at baseline at 2 and 8 weeks post-MI, but was significantly increased 4 weeks post-MI. Scleraxis protein expression was down-regulated within the scar area of infarcted hearts when compared to control samples 2 and 4 weeks post-MI. Ski mRNA expression was up-regulated within the scar area of infarcted hearts 2, 4 and 8 weeks after infarction. Conclusions: Scleraxis protein is down-regulated in myofibroblasts of the infarct scar in the chronic stages of myocardial infarction, corresponding to the maturation of the scar. At these stages of wound healing, we have previously published that Ski is up-regulated in the cytosol of these same cells. We suggest reciprocal feedback in the expression of these two proteins exists in myofibroblasts in the infarct scar. We hope to learn more about the Ski/Scleraxis feedback loop in pathological wound healing to identify novel therapeutic targets.

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