Structural arrangement of the cardiac collagen fibers of healthy and diabetic dogs

Benedicto, Hildebrando Gomes; Bombonato, Pedro Primo; Macchiarelli, Guido; Stifano, Giuseppe; Prado, Isaura Maria Mesquita

doi:10.1002/jemt.20988

Cited by 10 publications

(3 citation statements)

References 21 publications

(28 reference statements)

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“…[27][28][29] With the development of diabetes, myocardial fibrosis occurs accompanied with the increase of cardiac collagen fibers. 30 How to reverse myocardial fibrosis is of particular interest to researchers. Despite the presence of many therapies to decrease the degree of myocardial fibrosis, the effective measures are still lacking.…”

Section: Discussionmentioning

confidence: 99%

Effect of Irbesartan on AGEs-RAGE and MMPs systems in rat type 2 diabetes myocardial-fibrosis model

Cao

Fang

et al. 2019

Exp Biol Med (Maywood)

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To investigate the effect of Irbesartan on the changes of myocardial advanced glycation end products and their receptor (AGEs-RAGE), and matrix metalloproteinases (MMPs) systems in rat type 2 diabetes myocardial fibrosis model. All male Sprague-Dwaley rats were randomly divided into four groups: control (CON), high glucose and high-caloric diet (HC), type 2 diabetes (T2DM) and Irbesartan + T2DM (Ir+T2DM) groups. At 12th week, the fasting blood glucose (FBG) and fasting serum insulin (FINS) levels, insulin resistance index (IRI), insulin sensitivity index (ISI), body weight (BW), the ratio of heart weight/body weight (H/B), left ventricular weight index (LVWI), and cardiac col I, col III contents, plasma MMP-2, MMP-9 levels were evaluated. The protein expressions of col I, AGE, RAGE, MMP-2, MMP-14, and TIMP-2 were analyzed by Western blot. In the T2DM group, FBG, H/B, LVWI, IRI were increased ( P < 0.01), while FINS, BW, ISI were decreased in contrast to the CON and HC groups ( P < 0.05–0.01). In the Ir+ T2DM group, BW was higher, IRI, H/B, LVWI were lower than in the T2DM group. Compared with the CON and HC groups, the contents of col I and col III, the protein expressions of col I, AGE, RAGE, TIMP-2 and MMP-14 were increased, MMP-2 protein expression, the ratios of MMP-2/TIMP-2 and MMP-14/TIMP-2, MMP-2, and MMP-9 levels were decreased in the T2DM group ( P < 0.01). After Irbesartan treatment, all parameters were reversed. Irbesartan can ameliorate myocardial fibrosis in type 2 diabetes rat model, the likely mechanisms may be related to the down-regulation of AGEs-RAGE system and changes of MMPs pathway. Impact statement There are about 425 million diabetes patients (20–79 years) in the world according to the International Diabetes Federation Diabetes Atlas – 8th Edition. The cardiovascular complication is one of the major causes of death in diabetes patients. Myocardial fibrosis is one of the serious pathological changes, so investigating the pathogenesis of myocardial fibrosis has the significant value. Our study aims to investigate the effect of Irbesartan (the angiotensin II receptor antagonist) on the changes of AGE-RAGE system and MMP family components, and analyzes the potential mechanisms in type 2 diabetes-induced myocardial fibrosis. Our results provide the theoretical base for better understanding the pathogenesis in type 2 diabetes-induced myocardial complication. It is useful for clinicians to select the effective therapeutic measures for treatment of type 2 diabetes-induced organ fibrosis.

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Section: Discussionmentioning

confidence: 99%

Effect of Irbesartan on AGEs-RAGE and MMPs systems in rat type 2 diabetes myocardial-fibrosis model

Cao

Fang

et al. 2019

Exp Biol Med (Maywood)

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“…The average fiber diameter was around 150 nm in both the 1 and 1.5% concentrations. Such fiber dimensions are in accordance with endomysial fibers of the native cardiac matrix, which wrap individual cells and connect adjacent myocytes to one another [52,53]. Therefore, this system could provide the structural signaling needed for encapsulated cell attachment and enhance their survival until the delivery vehicle is degraded and the cells are integrated within the desired location.…”

Section: Scanning Electron Microscopymentioning

confidence: 92%

Omentum ECM-based hydrogel as a platform for cardiac cell delivery

Shevach¹,

Zax²,

Abrahamov³

et al. 2015

Biomed. Mater.

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Cardiovascular diseases remain the number one killer in Western countries. Despite recent advances and promising results in cardiac cell-based therapy, one of the remaining challenges is poor cell retention in the desired site. As a solution, cell delivery systems are developed to ensure that a sufficient number of viable cells reach the infarct area. These delivery systems are based on biomaterials that provide a surrogate microenvironment for the encapsulated cells, retaining them in the desired location post-delivery. Injectable thermoresponsive ECM-based hydrogels have been developed to achieve this goal. Unfortunately, the use of allogeneic or xenogeneic ECM may hamper the treatment due to an immune response to residual cellular content from the host. In this work, we have developed an omentum-based hydrogel capable of self-assembly under physiological conditions. Although in this study the omentum was obtained from porcine sources, it can be easily and safely extracted from the patient, serving as an autologous protective vehicle for the transported cells. We have characterized the biochemical composition, mechanical properties, and gelation and degradation kinetics of the processed biomaterial. Furthermore, the ability of the hydrogel to encapsulate cardiac cells and support their culture was evaluated. We envision that the newly developed platform may open new opportunities for personalized cell delivery to the heart and other tissues.

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“…Overall, the decellularized matrix contained fibers ranging from 150 nm to several micrometers in diameter (figure 3(d)). A matrix composed of such fiber dimensions may serve as an appropriate scaffold for engineering cardiac tissues, as these dimensions are in accordance with the endomysial and perimysial fibers of the native cardiac matrix, wrapping individual cardiomyocytes and cell bundles, respectively [46,47]. decellularization process.…”

Section: Decellularization Of the Omentum And Matrix Analysesmentioning

confidence: 99%

Fabrication of omentum-based matrix for engineering vascularized cardiac tissues

Shevach¹,

Soffer-Tsur²,

Fleischer³

et al. 2014

Biofabrication

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Fabricating three-dimensional, biocompatible microenvironments to support functional tissue assembly remains a key challenge in cardiac tissue engineering. We hypothesized that since the omentum can be removed from patients by minimally invasive procedures, the obtained underlying matrices can be manipulated to serve as autologous scaffolds for cardiac patches. Here we initially characterized the structural, biochemical and mechanical properties of the obtained matrix, and demonstrated that cardiac cells cultivated within assembled into elongated and aligned tissues, generating a strong contraction force. Co-culture with endothelial cells resulted in the formation of blood vessel networks in the patch without affecting its function. Finally, we have validated that omental scaffolds can support mesenchymal and induced pluripotent stem cells culture, thus may serve as a platform for engineering completely autologous tissues. We envision that this approach may be suitable for treating the infarcted heart and may open up new opportunities in the broader field of tissue engineering and personalized regenerative medicine.

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Structural arrangement of the cardiac collagen fibers of healthy and diabetic dogs

Cited by 10 publications

References 21 publications

Effect of Irbesartan on AGEs-RAGE and MMPs systems in rat type 2 diabetes myocardial-fibrosis model

Effect of Irbesartan on AGEs-RAGE and MMPs systems in rat type 2 diabetes myocardial-fibrosis model

Omentum ECM-based hydrogel as a platform for cardiac cell delivery

Fabrication of omentum-based matrix for engineering vascularized cardiac tissues

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