pectins and Myocardial-Infarction

Myocardial ischemia/reperfusion (IR) injury is caused by the restoration of the coronary blood flow following an ischemic episode. Accumulating evidence suggests that galectin-3, a β-galactoside-binding lectin, acts as a biomarker in heart disease. However, it remains unclear whether manipulating galectin-3 affects the susceptibility of the heart to IR injury. In this study, RNA sequencing (RNA-seq) analysis identified that Lgals3 (galecin-3) plays an indispensable role in IR-induced cardiac damage. Immunostaining and immunoblot assays confirmed that the expression of galectin-3 was markedly increased in myocardial IR injury both in vivo and in vitro. Echocardiographic analysis showed that cardiac dysfunction in experimental IR injury was significantly attenuated by galectin-3 inhibitors including pectin (1%, i.p.) from citrus and binding peptide G3-C12 (5.0 mg/kg, i.p.). Galectin-3 inhibitor-treated mice exhibited smaller infarct sizes and decreased tissue injury. Furthermore, TUNEL staining showed that galectin-3 inhibition suppressed IR-mediated cardiomyocyte apoptosis. Mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (mPTP) levels were well-preserved and IR-induced changes of mitochondrial cyto c, cytosol cyto c, caspase-9, caspase-3, Bcl-2 and Bax in the galectin-3 inhibitor-treated groups were observed. Our findings indicate that the pathological upregulation of galectin-3 contributes to IR-induced cardiac dysfunction and that galectin-3 inhibition ameliorates myocardial injury, highlighting its therapeutic potential.

Topics: Animals; Apoptosis; Cardiotonic Agents; Cell Line; Galectin 3; Heart; Homeostasis; Male; Mice; Mice, Inbred C57BL; Mitochondria; Myocardial Infarction; Myocardial Reperfusion Injury; Pectins; Peptides; Up-Regulation

Although optimal therapy for myocardial infarction includes reperfusion to restore blood flow to the ischemic region, ischemia/reperfusion (IR) also initiates an inflammatory response likely contributing to adverse left ventricular (LV) extracellular matrix (ECM) remodeling. Galectin-3 (Gal-3), a β-galactoside-binding-lectin, promotes cardiac remodeling and dysfunction. Our aim is to investigate whether Gal-3 pharmacological inhibition using modified citrus pectin (MCP) improves cardiac remodeling and functional changes associated with IR. Wistar rats were treated with MCP from 1 day before until 8 days after IR (coronary artery ligation) injury. Invasive hemodynamics revealed that both LV contractility and LV compliance were impaired in IR rats. LV compliance was improved by MCP treatment 8 days after IR. Cardiac magnetic resonance imaging showed decreased LV perfusion in IR rats, which was improved with MCP. There was no difference in LV hypertrophy in MCP-treated compared to untreated IR rats. However, MCP treatment decreased the ischemic area as well as Gal-3 expression. Gal-3 blockade paralleled lower myocardial inflammation and reduced fibrosis. These novel data showing the benefits of MCP in compliance and ECM remodeling in IR reinforces previously published data showing the therapeutic potential of Gal-3 inhibition.

Topics: Animals; Biomarkers; Blood Proteins; Disease Models, Animal; Galectin 3; Galectins; Gene Expression; Heart Failure; Heart Function Tests; Immunohistochemistry; Magnetic Resonance Imaging; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Pectins; Rats

The development of coronary heart disease can be divided into preocclusion and postocclusion steps. We previously showed that cell wall polysaccharides consisting of a high content of arabinose and/or xylose, such as apple pectin, protected against myocardial injury by inhibiting postocclusion steps. We hypothesized that xyloglucan, another apple cell wall polysaccharide that consists of a high content of xylose, might also show myocardial protection. To test the hypothesis, rats were supplemented with either tamarind xyloglucan (TXG) (1, 10, and 100 mg/kg per day) or cotton cellulose (CCL) (100mg/kg per day) for 3 days. Then, rats underwent 30 minutes of ischemia followed by 3 hours of reperfusion. Supplementation with TXG at a dosage greater than 10mg/kg per day significantly reduced the infarct size (IS), whereas supplementation with CCL at 100mg/kg per day did not reduce IS. TXG supplementation up-regulated the expression of myoglobin and fatty acid-binding protein, both of which are known to be involved in apoptosis and ATP generation. Indeed, TXG supplementation inhibited apoptosis through decrease in p38 and JNK phosphorylation, increase in Bcl-2/Bax ratio, inhibition in the conversion of procaspase-3 to cleaved caspase-3, and decrease in the generation of DNA nicks. From these results, we demonstrated that xyloglucan in apple can protect against myocardial injury by inhibiting apoptosis and improving energy metabolism. Therefore, apple xyloglucan and pectin contribute to the known beneficial effects of apple in reducing the risk of coronary heart disease by blocking postocclusion steps through apoptosis inhibition. In addition, this study demonstrates the feasibility of developing TXG as a cardioprotectant.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Cardiotonic Agents; Caspase 3; Cell Wall; Diet; Disease Models, Animal; Energy Metabolism; Fruit; Glucans; In Situ Nick-End Labeling; Male; Malus; Mitogen-Activated Protein Kinases; Myocardial Infarction; Myocardium; Pectins; Phosphorylation; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Tamarindus; Xylans