Regional protein expression changes within the left ventricle in a mouse model of dyssynchronous and resynchronized heart failure
ESC HEART FAILURE
Authors: Nordin, Hugo; Nakagawa, Ryo; Wallin, Marita; Pernow, John; Kass, David A.; Stahlberg, Marcus
Abstract
Aims The biological mechanisms conveying the salutary effects of cardiac resynchronization therapy in heart failure remain elusive. We have recently developed a mouse model of heart failure with dyssynchrony/resynchronization. The aim of this study was to characterize regional left ventricular heterogeneity in protein expression comparing early (septum) and late (lateral) activated left ventricular wall segments in synchronous (SHF), dyssynchronous (DHF), and resynchronized heart failure (RHF). Methods and results Mice subjected to ischaemia/reperfusion were divided into three groups: sinus rhythm for 4 weeks (SHF), right ventricular pacing for 4 weeks (DHF), and right ventricular pacing for 2 weeks and 2 weeks of sinus rhythm (RHF). Relative concentrations of 92 proteins from septal and lateral left ventricular wall segments (n = 10 per group) were compared within each group. We also analysed the effect of DHF vs. SHF and RHF vs. DHF on protein expression pattern comparing the same left ventricular segments between the groups. Proteins with significantly differential expression between left ventricular segments were analysed for protein-protein correlations, protein-protein interactions, and biological and signalling pathways. Eight proteins were significantly down-regulated in the late activated (compared with early activated) lateral wall uniquely in RHF (P < 0.05 adjusted for a 5% false discovery rate): Erbb4, Ntf3, Pdgfb, Tnf, Notch3, Qdpr, Tpp1, and Itgb6. Protein correlation matrix showed that six of these were strongly and positively correlated and five had known protein-protein interactions. Biological pathways mainly down-regulated in late activated myocardium in RHF were MAPK signalling and hypertrophic cardiomyopathy. There were no significantly differentially expressed proteins comparing the same left ventricular segments between the DHF and SHF (range of P-values: 0.05-1.00) and RHF and DHF (range of P-values: 0.32-1.00). Conclusions In a mouse model of heart failure with dyssynchrony and resynchronization, we observed down-regulation of several proteins in the late activated lateral wall, compared with the septum, in resynchronized mice. These proteins display significant protein-protein correlation and share biological signalling pathways, including MAPK activation and hypertrophy signalling.
Anti-psoriatic effect of Lavandula angustifolia essential oil and its major components linalool and linalyl acetate
JOURNAL OF ETHNOPHARMACOLOGY
Authors: Rai, Vineet Kumar; Sinha, Priyam; Yadav, Kuldeep Singh; Shukla, Aparna; Saxena, Archana; Bawankule, Dnyaneshwar Umrao; Tandon, Sudeep; Khan, Feroz; Chanotiya, Chandan Singh; Yadav, Narayan Prasad
Abstract
Ethno-pharmacological relevance: Lavender oil (LO) is an aromatic/essential oil extracted from Lavandula angustifolia and traditionally used as an aromatherapy massage oil due to its anti-inflammatory and wound healing property and also for providing the relief in other skin conditions such as psoriasis, dermatitis and eczema. However, LO has not been evaluated scientifically for psoriasis like skin inflammation. Aim of the study: This study was aimed to investigate the LO and its major components linalool (L) and linalyl acetate (LA) against psoriasis like skin inflammation. Materials and methods: Anti-psoriatic activity was done using Imiquimod (IMQ) induced psoriasis like skin inflammation in BALB/c mice. Assessment of anti-psoriatic effect of LO, L and LA was done on the basis of change in ear thickness, psoriasis area severity index (PASI) scoring at alternative day, CosCam scoring using skin analyzer equipped with SkinSys software, biochemical, immunohistochemical and histological investigations. Level of effectiveness against psoriasis was investigated by percent reduction in PASI scores, CosCam scores and level of Th-1 and Th-17 cell expressing cytokines, as compared to the diseased mice. Results: Topical application of LO 10% showed 73.67% recovery in PASI and 87% in Th-17 cell-specific cytokines towards normal as compared to disease group. L and LA were identified as the major components of LO and favoured ligands for selected psoriasis targets. At 2% topical dose, L and LA showed 64% and 47.61% recovery in PASI scores, respectively. Both, L and LA showed significant recovery in Th-1 specific TNF-alpha and IL-1 beta however, only L showed significant recovery of Th-17 cytokines (IL-17 and IL-22). In contrast to LA (which restored granulosis), L restored epidermal hyperplasia and parakeratosis toward the normal condition. On the other hand, L also reduced the expression of NF-kappa beta, ccr6 and IL-17, while LA reduced the expression of NE-kappa beta only. At 10% topical dose, LO was observed to be slight irritant while at 2% topical dose, L and LA were found non-irritant to the skin. Conclusion: This study proves the effectiveness of LO and its major phytoconstituents linalool and linalyl acetate against IMQ induced psoriasis like skin inflammation and provides the scientific evidence for topical use of lavender oil.