Different heart failure phenotypes of valvular heart disease: the role of mitochondrial dysfunction

Valvular heart disease (VHD)-related heart failure (HF) is a special subtype of HF with an increasingly concerned heterogeneity in pathophysiology, clinical phenotypes, and outcomes. The mechanism of VHD-related HF involves not only mechanical damage to the valve itself but also valve lesions caused by myocardial ischemia. The interactions between them will lead to the occurrence and development of VHD-related HF subtypes. Due to the spatial (combination of different valvular lesions) and temporal effects (sequence of valvular lesions) of valvular damages, it can make the patient's condition more complicated and also make the physicians deal with a dilemma when deciding on a treatment plan. This indicates that there is still lack of deep understanding on the pathogenic mechanism of VHD-related HF subtypes. On the other hand, mitochondrial dysfunction (MitD) is not only associated with the development of numerous cardiac diseases such as atherosclerosis, hypertension, diabetes, and HF but also occurs in VHD. However, the role of MitD in VHD-related HF is still not fully recognized. In this comprehensive review, we aim to discuss the current findings and challenges of different valvular damages derived from HF subtypes as well as the role of MitD in VHD-related HF subtypes

ACE2 polymorphisms associated with cardiovascular risk in Uygurs with type 2 diabetes mellitus

Abstract Background Type 2 diabetes mellitus (T2D), rapidly increasing to epidemic proportions, globally escalates cardiovascular disease risk. Although intensive interventions and comprehensive management of environmental risks factors for T2D are associated with reduced cardiovascular disease, such approaches are limited for individuals with high genetic T2D risk. In this study we investigated possible associations of ACE2 polymorphisms and cardiovascular risks in Uygur patients with T2D. Methods 275 Uygur T2D patients and 272 non-diabetic Uygur individuals were enrolled as study participants. 14 ACE2 polymorphisms were genotyped by Matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Results ACE2 SNP rs1978124, rs2048683, rs2074192, rs233575, rs4240157, rs4646156, rs4646188 and rs879922 were associated with T2D (all P < 0.05). The 8 diabetic risk related ACE2 SNPs were further associated with diabetic related cardiovascular complications or events but exhibited heterogeneity as fellows: firstly, almost all diabetic risk related ACE2 SNPs (all P < 0.05) were associated with increased SBP except rs1978124 and rs2074192, while rs2074192, rs4646188 and rs879922 were associated elevated DBP (all P < 0.05). Secondly, SNP rs4646188 was not correlated with any type of dyslipidemia (TRIG, HDL-C, LDL-C or CHOL), and the other 7 diabetic risk related loci were at least correlated with one type of dyslipidemia (all P < 0.05). In particular, rs879922 were simultaneously correlated with four type of dyslipidemia (all P < 0.05). Thirdly, ACE2 SNP rs2074192 and rs879922 were associated with carotid arteriosclerosis stenosis (CAS) ≥ 50% (both P < 0.05). Fourthly, ACE2 SNP rs2074192, rs4240157, rs4646188 and 879922 were associated with increased MAU (all P < 0.05). In addition, ACE2 SNP rs2048683, rs4240157, rs4646156, rs4646188 and rs879922 were linked to heavier LVMI (all P < 0.05), but only rs4240157, rs4646156 and rs4646188 were associated with lower LVEF (all P < 0.05). Conclusion ACE2 SNP rs879922 may be a common genetic loci and optimal genetic susceptibility marker for T2D and T2D related cardiovascular risks in Uygurs

Image1_Edible bird’s nest, an Asian health food supplement, possesses anti-inflammatory responses in restoring the symptoms of atopic dermatitis: An analysis of signaling cascades.TIF

Edible bird’s nest (EBN) is a Chinese delicacy possessing skin rejuvenating functions. To verify skin anti-inflammatory function of EBN, water extract and enzymatic digest of EBN, as well as the major sialic acid, N-acetyl neuraminic acid (NANA), were probed in TNF-α-treated HaCaT keratinocytes. The mRNA expressions of pro-inflammatory cytokines, e.g., IL-1β, IL-6, TNF-α, and an enzyme responsible for inflammatory response, i.e., Cox-2, as well as filaggrin and filaggrin-2, were markedly altered after treating with different preparations of EBN. The EBN-mediated responses could be accounted by its robust reduction of reactive oxygen species (ROS), NF-κB signaling and phosphorylation of p38 MAPK and JNK, as triggered by TNF-α-induced inflammation. The anti-inflammatory response of EBN was further supported in animal model. In 2,4-dinitrochlorobenzene (DNCB)-induced dermatitic mice, the effects on skin thickness, severity level of damage and scratching behavior, exerted by DNCB, were reversed after EBN treatments, in dose-dependent manners. In parallel, the levels of immune cells and pro-inflammatory cytokines in dermatitic skin were markedly reduced by treatment of EBN preparations. In general, NANA and enzymatic digest of EBN showed better anti-inflammatory responses in both models of in vitro and in vivo. These lines of evidence therefore suggest the possible application of EBN in treating atopic dermatitis.</p

Image2_Edible bird’s nest, an Asian health food supplement, possesses anti-inflammatory responses in restoring the symptoms of atopic dermatitis: An analysis of signaling cascades.tif

Edible bird’s nest (EBN) is a Chinese delicacy possessing skin rejuvenating functions. To verify skin anti-inflammatory function of EBN, water extract and enzymatic digest of EBN, as well as the major sialic acid, N-acetyl neuraminic acid (NANA), were probed in TNF-α-treated HaCaT keratinocytes. The mRNA expressions of pro-inflammatory cytokines, e.g., IL-1β, IL-6, TNF-α, and an enzyme responsible for inflammatory response, i.e., Cox-2, as well as filaggrin and filaggrin-2, were markedly altered after treating with different preparations of EBN. The EBN-mediated responses could be accounted by its robust reduction of reactive oxygen species (ROS), NF-κB signaling and phosphorylation of p38 MAPK and JNK, as triggered by TNF-α-induced inflammation. The anti-inflammatory response of EBN was further supported in animal model. In 2,4-dinitrochlorobenzene (DNCB)-induced dermatitic mice, the effects on skin thickness, severity level of damage and scratching behavior, exerted by DNCB, were reversed after EBN treatments, in dose-dependent manners. In parallel, the levels of immune cells and pro-inflammatory cytokines in dermatitic skin were markedly reduced by treatment of EBN preparations. In general, NANA and enzymatic digest of EBN showed better anti-inflammatory responses in both models of in vitro and in vivo. These lines of evidence therefore suggest the possible application of EBN in treating atopic dermatitis.</p