Recent Advances in Nanomaterials for Therapy and Diagnosis of Cardiovascular Disease

Cardiovascular diseases (CVDs) are among the world’s widely affected disorders, including ischemia and stroke. Acute Myocardial ischemia (AMI) is a deadly disease caused by irreversible damage to the left ventricular heart tissues. The thromboembolic plaque stops the oxygen supply to the main blood vessels and ventricles. During chronic inflammation, myocardial infarction and free radicals damage stable myocardium, smooth muscles cell, and epithelial cells caused by outer membrane loss and ventricular wall smoothing and dilation. Specially constructed scaffolds made of biological and nanoparticles have been created to shield the left ventricle from further injury and recover ischemic endothelial cells. Preclinical experiments have demonstrated that scaffolds containing growth factors and cells will regenerate ischemic tissue into a stable pericardium in good working order. Various medicinal approaches that treat cardiovascular disease conditions at different stages are discussed in this review article, with biomaterials receiving special attention. This review further addresses the manipulation and manufacturing of biomedical implantable devices using nanomedicine methods and drug delivery principles. The use of graphene and exosomal nanovesicle in cardiovascular therapeutics recently progressed in research studies.

Influence of Intrinsic Aerobic Exercise Capacity and Sex on Cardiac Injury Following Acute Myocardial Ischemia and Reperfusion

Purpose: Previous reports have suggested that active exercise aside, intrinsic aerobic running capacity (Low = LCR, high = HCR) in otherwise sedentary animals may influence several cardiovascular health-related indicators. Relative to the HCR phenotype, the LCR phenotype is characterized by decreased endothelial reactivity, increased susceptibility to reperfusion-induced arrhythmias following short, non-infarction ischemia, and increased diet-induced insulin resistance. More broadly, the LCR phenotype has come to be characterized as a “disease prone” model, with the HCRs as “disease resistant.” Whether these effects extend to injury outcomes in an overt infarction or whether the effects are gender specific is not known. This study was designed to determine whether HCR/LCR phenotypic differences would be evident in injury responses to acute myocardial ischemia-reperfusion injury (AIR), measured as infarct size and to determine whether sex differences in infarction size were preserved with phenotypic selection.Methods: Regional myocardial AIR was induced in vivo by either 15 or 30 min ligation of the left anterior descending coronary artery, followed by 2 h of reperfusion. Global ischemia was induced in isolated hearts ex vivo using a Langendorff perfusion system and cessation of perfusion for either 15 or 30 min followed by 2 h of reperfusion. Infarct size was determined using 2, 3, 5–triphenyltetrazolium chloride (TTC) staining, and normalized to area at risk in the regional model, or whole heart in the global model. Portions of the tissue were paraffin embedded for H&E staining and histology analysis.Results: Phenotype dependent differences in infarct size were seen with 15 min occlusion/2 h reperfusion (LCR > HCR, p < 0.05) in both regional and global models. In both models, longer occlusion times (30 min/2 h) produced significantly larger infarctions in both phenotypes, but phenotypic differences were no longer present (LCR vs. HCR, p = n.s.). Sex differences in infarct size were present in each phenotype (LCR male > LCR female, p < 0.05; HCR male > HCR female, p < 0.05 regardless of length of occlusion, or ischemia model.Conclusions: There is cardioprotection afforded by high intrinsic aerobic capacity, but it is not infinite/continuous, and may be overcome with sufficient injury burden. Phenotypic selection based on endurance running capacity preserved sex differences in response to both short and longer term coronary occlusive challenges. Outcomes could not be associated with differences in system characteristics such as circulating inflammatory mediators or autonomic nervous system influences, as similar phenotypic injury patterns were seen in vivo, and in isolated crystalloid perfused heart ex vivo.

Uncoupling protein 1 knockout aggravates isoproterenol-induced acute myocardial ischemia via AMPK/mTOR/PPARα pathways in rats

Uncoupling protein 1 (UCP1) was found exclusively in the inner membranes of the mitochondria of brown adipose tissue (BAT). We found that UCP1 was also expressed in heart tissue and significantly upregulated in isoproterenol (ISO)-induced acute myocardial ischemia (AMI) rat model. The present study is to determine the underlying mechanism involved in the UCP1 upregulation in ISO-induced AMI rat model. The Ucp1−/− rats were generated by CRISPR-Cas9 system and presented decreased BAT volume. 2-months old Sprague Dawley (SD) wild-type (WT) and Ucp1−/− rats were treated with ISO intraperitoneally 30 mg/kg once a day for 3 consecutive days to establish AMI model. In saline group, the echocardiographic parameters, serum markers of myocardial injury cardiac troponin I (cTnI), creatine kinase isoenzyme MB (CK-MB), oxidant malondialdehyde (MDA), antioxidant superoxide dismutase (SOD) or fibrosis were comparable between WT and Ucp1−/− rats. ISO treatment induced worse left ventricle (LV) hypertrophy, myocardial fibrosis, increased higher cTnI, CK-MB and MDA and decreased lower SOD level in Ucp1−/− rats compared with that of WT rats. Ucp1−/− rats also presented lower myocardial phosphocreatine (PCr)/ATP-ratio, which demonstrated worse cardiac energy regulation defect. ISO treatment induced the phosphorylation of AMP-activated protein kinase (AMPK) activation, subsequently the phosphorylation of mammalian target of rapamycin (mTOR) inhibition and peroxisome proliferators-activated receptor α (PPARα) activation in WT rats, whereas activation of AMPK/mTOR/PPARα pathways significantly inhibited in Ucp1−/− rats. To sum up, UCP1 knockout aggravated ISO-induced AMI by inhibiting AMPK/mTOR/PPARα pathways in rats. Increasing UCP1 expression in heart tissue may be a cytoprotective therapeutic strategy for AMI.

Study on the Effects of Kuanxiong Aerosol on the Isolated Artery and Rabbits Acute Myocardial Ischemia Model

Background: Kuan xiong aerosol (KXA) is a kind of Chinese herbal compound used to regulating qi-flowing for relieving pain and improving angina. However, little pharmacological study of this traditional Chinese medicine preparation has been reported to confirm these activities. Objective: This article aims to observe the effect of resisting acute myocardial ischemia (AMI) in vivo and dilating vessel in vitro of KXA. Materials: The AMI model involves intravenously injecting pituitary (2 U.kg-1) into the ear of rabbits. Electrocardiograph (ECG) T waves were then recorded after administration and the falling range was calculated. Following this, the level of serum Cardiac troponin T (cTn-T) and the histopathology of the cardiac muscle tissue was evaluated. In vitro, the effect of KXA on vasodilation of isolated aortic rings that had been pre-contracted with KCl (30 mM) was observed. Results: It was found KXA reduced ECG ST-T waves and serum cTn-T in the rabbit AMI model, protected myocardial tissue from fracturing and loss of myocardial fibers, and inhibited inflammatory cell infiltration, cavitation degeneration and karyopyknosis of the myocardial matrix. Furthermore, the administration of 0.215, 1.075 and 2.150 mg.mL-1 KXA resulted in significant relaxation of the aortic rings at a rate of 69.63 %, 90.14 % and 118.72 % (p < 0.01) of the untreated ones, and a second shrinkage ratio of 20.17 %, 4.29 %, and 4.54 % (p < 0.01) of the untreated ones, respectively. Conclusions: these results suggest KXA protects against AMI, contributes to dilation of blood vessels and has long-acting effectiveness.

Uncovering the Protective Mechanism of the Volatile Oil of Acorus tatarinowii against Acute Myocardial Ischemia Injury Using Network Pharmacology and Experimental Validation

Acorus tatarinowii is a traditional aromatic resuscitation drug that can be clinically used to prevent cardiovascular diseases. The volatile oil of Acorus tatarinowii (VOA) possesses important medicinal properties, including protection against acute myocardial ischemia (MI) injury. However, the pharmacodynamic material basis and molecular mechanisms underlying this protective effect remain unclear. Using network pharmacology and animal experiments, we studied the mechanisms and pathways implicated in the activity of VOA against acute MI injury. First, VOA was extracted from three batches of Acorus tatarinowii using steam distillation, and then, its chemical composition was determined by GC-MS. Next, the components-targets and protein-protein interaction networks were constructed using systematic network pharmacology. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were also conducted in order to predict the possible pharmacodynamic mechanisms. Furthermore, animal experiments including ELISAs, histological examinations, and Western blots were performed in order to validate the pharmacological effects of VOA. In total, 33 chemical components were identified in VOA, and ß-asarone was found to be the most abundant component. Based on network pharmacology analysis, the therapeutic effects of VOA against myocardial ischemia might be mediated by signaling pathways involving COX-2, PPAR-α, VEGF, and cAMP. Overall, the obtained results indicate that VOA alleviates the pathological manifestations of isoproterenol-hydrochloride-induced myocardial ischemia in rats, including the decreased SOD (superoxide dismutase) content and increased LDH (lactic dehydrogenase) content. Moreover, the anti-MI effect of VOA might be attributed to the downregulation of the COX-2 protein that inhibits apoptosis, the upregulation of the PPAR-α protein that regulates energy metabolism, and the activation of VEGF and cAMP signaling pathways.