Ghrelin ameliorated inflammation and oxidative stress in isoproterenol induced myocardial infarction through the endothelial nitric oxide synthase (eNOS)/nuclear factor erythroid 2-related factor-2 (NRF2)/heme oxygenase-1 (HO-1) signaling pathway.

Although there is accumulating evidence which suggests that the administration of ghrelin could be used to preserve cardiac function, delay the progression of heart failure post-myocardial infarction, and attenuate ventricular remodeling, there is still no definitive data that clearly highlights the mechanisms by which ghrelin exerts cardioprotective effects. The present study aimed to investigate whether ghrelin could affect nuclear factor erythroid 2-related factor-2 (Nrf2), heme oxygenase-1 (HO-1), and endothelial nitric oxide synthase (eNOS) expression and exert anti-inflammatory as well as antioxidant-like actions through this signaling pathway. Rats were assorted into four groups with 10 in each: Group I (Control), Group II (received ghrelin only), Group III (MI was induced by isoproterenol (ISO)), Group IV (MI was induced by isoproterenol and within 30 min of each ISO dose, rats received ghrelin; 100 µg /kg subcutaneously two times per day). We assessed the effects of acylated ghrelin on the biochemical changes, ECG parameters, heart rate, histopathological scoring and the mRNA expression of eNOS, Nrf2 (confirmed immunohistochemically) as well as HO-1 genes in the cardiac tissues. Nuclear factor-κB, tumor necrosis factor-α, interleukin-6, and inducible nitric oxide synthase were assessed as inflammatory markers. Ghrelin markedly improved the oxidative stress injury and inflammation, showed histological preservation of the cardiac muscle fibers morphology, ameliorated the ISO-induced ECG changes and caused a significant elevation in eNOS, HO-1, and Nrf2 expression. In conclusion, ghrelin exerts cardioprotective effect in ISO-induced myocardial infarction by promoting the eNOS/Nrf2/HO-1 pathway.

Citicoline improved cardiovascular function in animal model of dysautonomia.

The autonomic nervous system controls cardiovascular function. Autonomic dysfunction or dysautonomia is commonly encountered in several diseases like Parkinson's disease. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a chemical that changes into the neurotoxin MPP+, which causes catecholamine depletion. We aimed to study the effects of citicoline on cardiovascular function in MPTP-treated albino rats. Twenty-four male albino rats were divided into four groups (6 rats/group): negative control received intraperitoneal (i.p.) saline injection for five consecutive days, a positive control (Citicoline group) received citicoline (250 mg/kg) by oral gavage for consecutive 20 days, MPTP treated with MPTP-HCL (30 mg/kg, i.p.) for five consecutive days, MPTP + citicoline treated with MPTP-HCL (30 mg/kg, i.p.) for five consecutive days followed by treatment with oral doses of citicoline (250 mg/kg) for 20 days. Cardiovascular functions evaluated through recording electrocardiogram (ECG), echocardiography, measuring arterial blood pressure and assessment of aortic rings vascular reactivity. Biochemical measurements on cardiac tissue for tyrosine hydroxylase, norepinephrine, glucose transporter 1 (GLUT1), insulin receptor substrate 1 (IRS1), peroxisome proliferator-activated receptor γ co-activator-1 (PPAR-γ co-activator-1) (PGC-1), phosphatase and tensin homolog-induced kinase 1 (PINK1), carnitine palmitoyltransferase I (CPT1), uncoupling protein 2 (UCP2) and adenosine monophosphate-activated protein kinase alpha 2 (AMPKα2). Citicoline increased cardiac norepinephrine and tyrosine hydroxylase and improved markers related to ROS scavenger, mitochondrial permeability, calcium homeostasis on the cellular level, metabolic homeostasis, and mitochondrial biogenesis. We conclude that citicoline improved cardiovascular dysautonomia and that was reflected on cardiac contractility, electrical activity, blood pressure, and vascular reactivity.

Role of extracellular matrix remodelling gene SNPs in keratoconus.

Introduction: Single nucleotide polymorphisms (SNPs) in genes for certain structural components may be implicated in the pathogenesis of keratoconus. We hypothesized links between SNPs in genes coding for collagen, matrix metalloproteinase 9 (MMP9) and tissue inhibitor of matrix metalloproteinase (TIMP) and keratoconus. Furthermore, we hypothesized links between MMP-9 and TIMP-1 SNPs and their tear level in keratoconus patients.Materials and methods: We genotyped 200 keratoconus and 100 control subjects by allele-specific PCR, and quantified MMP-9 and TIMP1 in tear samples by ELISA.Results: COL4A3 (rs55703767) and MMP-9 (rs17576) G alleles were over-represented in keratoconus patients (P < 0.01). TIMP-1 (rs6609533) A allele was more prevalent in keratoconus females (P < 0.01) but not in males (P = 0.73). MMP-9 was higher (P < 0.001) and TIMP1 lower (P < 0.001) in tear samples from keratoconus patients compared to controls. Keratoconus cases carrying MMP-9 (rs17576) homozygous (GG) alleles had higher tear MMP-9 compared to those carrying the (A) allele (P < 0.01). Females carrying TIMP-1 (rs6609533) homozygous (AA) alleles in both groups had significantly lower tear TIMP-1 compared to carriers of the AG and GG genotypes.Conclusions: This study supports the hypothesis of a functional role for COL4A3 (rs55703767, G/T), MMP-9 (rs17576, A/G) and TIMP-1 (rs6609533, A/G) SNPs in the pathogenesis of keratoconus.

miR-15a: a potential diagnostic biomarker and a candidate for non-operative therapeutic modality for age-related cataract.

Introduction: In order to better understand the role of hsa-miR-15a in the pathogenesis of age-related cataracts, we hypothesised altered expression, and of target anti-apoptotic genes, BCL-2 and MCL-1, in lens epithelial cells amongst age-related cataract patients.Material and methods: Reverse transcription quantitative polymerase chain reaction (RT-qPCR) quantified the expression of hsa-miR-15a and the target genes BCL-2 and MCL-1 in lens epithelial cells of 120 age-related cataract patients (40 patients with cortical cataracts, 40 patients with nuclear cataracts and 40 patients with posterior subcapsular cataracts) and 40 controls. Sixty specimens (15 normal and 45 cataracts) were stained immunohistochemically with BCL-2 and MCL-1 markers.Results: The expression of hsa-miR-15a was significantly increased (p = 0.003) in lens epithelial cells of cataract patients compared to the control group. BCL-2 and MCL-1 expression levels were significantly decreased in cataract patients (p < 0.001). A significant increase in hsa-miR-15a expression in the cortical subtype compared to the posterior subcapsular subtype (p = 0.003) and a significant decrease in BCL-2 and MCL-1 expressions in the cortical subtype compared to the nuclear and the posterior subcapsular subtype was detected.Conclusions: The increased expression of hsa-miR-15a in lens epithelial cells of cataract patients may repress the expression of BCL-2 and MCL-1. The expression of hsa-miR-15a and the subsequent apoptosis of lens epithelial cells are part of the pathogenesis of age-related cataracts.