Type 2 diabetes (T2D) is characterized by metabolic derangements that cause a shift in substrate preference, inducing cardiac interstitial fibrosis. Interstitial fibrosis plays a key role in ...aggravating left ventricular diastolic dysfunction (LVDD), which has previously been associated with the asymptomatic onset of heart failure. The latter is responsible for 80% of deaths among diabetic patients and has been termed diabetic cardiomyopathy (DCM). Through in silico prediction and subsequent detection in a leptin receptor-deficient db/db mice model (db/db), we confirmed the presence of previously identified potential biomarkers to detect the early onset of DCM. Differential expression of Lysyl Oxidase Like 2 (LOXL2) and Electron Transfer Flavoprotein Beta Subunit (ETFβ), in both serum and heart tissue of 6-16-week-old db/db mice, correlated with a reduced left-ventricular diastolic dysfunction as assessed by high-resolution Doppler echocardiography. Principal component analysis of the combined biomarkers, LOXL2 and ETFβ, further displayed a significant difference between wild type and db/db mice from as early as 9 weeks of age. Knockdown in H9c2 cells, utilising siRNA of either LOXL2 or ETFβ, revealed a decrease in the expression of Collagen Type I Alpha1 (COL1A1), a marker known to contribute to enhanced myocardial fibrosis. Additionally, receiver-operating curve (ROC) analysis of the proposed diagnostic profile showed that the combination of LOXL2 and ETFβ resulted in an area under the curve (AUC) of 0.813, with a cut-off point of 0.824, thus suggesting the favorable positive predictive power of the model and further supporting the use of LOXL2 and ETFβ as possible early predictive DCM biomarkers.
In pulmonary arterial hypertension (PAH), right ventricular (RV) dysfunction develops via mechanisms involving oxidative stress. Moderate and chronic red wine (RW) consumption reduces oxidative ...stress and confers cardioprotection but its effect on PAH is unknown. We evaluated whether moderate and chronic consumption of reduced-alcohol RW (RARW) confers cardioprotection in a monocrotaline (MCT)-induced PAH rat model.
Rats were randomly grouped: control; MCT; RARW; MCT + RARW. Wine was diluted to mimic moderate intake for humans, and consumed from 7 days before, until 28 days after MCT-injection. Echocardiography measured pulmonary artery acceleration time (PAAT) and RV thickness. Conjugated dienes (CD), and thiobarbituric acid reactive substances (TBARS) concentrations were assessed. MCT induced RV thickness and decreased PAAT compared to controls 1.22 ± 0.09 mm vs 0.46 ± 0.02 mm and 14 ± 1 vs 23 ± 2 m/s, respectively (p < 0.001). Chronic RARW consumption limited MCT-induced RV hypertrophy and increased PAAT. CD and TBARS increased in MCT-treated animals compared to controls (672 ± 43 nmol/L vs 453 ± 35 nmol/L; p < 0.01 and 13 ± 2 µmol/L vs 4 ± 0.3 µmol/L; p < 0.01). RARW reduced MCT-induced CD (472 ± 27 nmol/L vs 672 ± 43 nmol/L; p < 0.01).
Chronic and moderate intake of RARW ameliorates MCT-induced PAH in rats, which may be partly attributable to reduction of lipid peroxidation.
The survivor activating factor enhancement (SAFE) pathway was discovered as an alternative intrinsic pro-survival signaling pathway to the reperfusion injury salvage kinase pathway for ...cardioprotection against ischemia–reperfusion injury. The delineation of this pathway, made of key components such as cytokines of the immune system and transcription factors, has brought major advancements in our understanding on how the heart is able to protect itself against ischemia–reperfusion injury. In this viewpoint, we describe the major steps leading to the discovery of the SAFE pathway in small animal models to date and we discuss its translation to large animals and humans.
Although there is evidence linking sugar-sweetened beverage (SSB) intake with the development of cardio-metabolic diseases, the underlying mechanisms remain unclear. The current study therefore ...evaluated the effects of SSB consumption by establishing a unique in-house in vivo experimental model.
Male Wistar rats were divided into two groups: a) one consuming a popular local SSB (SSB- Jive), and b) a control group (Control-water) for a period of three and six months (n = 6 per group), respectively. Rats were gavaged on a daily basis with an experimental dosage amounting to half a glass per day (in human terms) (SSB vs. water). Cardiac function was assessed at baseline (echocardiography) and following ex vivo ischemia-reperfusion of the isolated perfused working rat heart. Oral glucose tolerance tests and mitochondrial respiratory analyses were also performed. In addition, the role of non-oxidative glucose pathways (NOGPs), i.e. the polyol pathway, hexosamine biosynthetic pathway (HBP) and PKC were assessed.
These data show that SSB intake: a) resulted in increased weight gain, but did not elicit major effects in terms of insulin resistance and cardiac function after three and six months, respectively; b) triggered myocardial NOGP activation after three months with a reversion after six months; and c) resulted in some impairment in mitochondrial respiratory capacity in response to fatty acid substrate supply after six months.
SSB intake did not result in cardiac dysfunction or insulin resistance. However, early changes at the molecular level may increase risk in the longer term.
Abstract Purpose Coronary artery bypass grafting (CABG) on cardiopulmonary bypass (CPB) is associated with myocardial ischemia–reperfusion injury (IRI), which may limit the benefit of the surgery. ...Both experimental and clinical studies suggest that Intralipid, a lipid emulsion commonly used for parenteral nutrition, can limit myocardial IRI. We therefore aimed to investigate whether Intralipid administered at reperfusion can reduce myocardial IRI in patients undergoing CABG on CPB. Methods We conducted a randomized, double-blind, pilot trial in which 29 adult patients scheduled for CABG were randomly assigned (on a 1:1 basis) to receive either 1.5 ml/kg Intralipid 20% or Ringer’s Lactate 3 min before aortic cross unclamping. The primary endpoint was the 72-h area under the curve (AUC) for troponin I. Results Of the 29 patients randomized, 26 were included in the study (two withdrew consent and one was excluded before surgery). The 72-h AUC for troponin I did not significantly differ between the control and Intralipid group (546437 ± 205518 versus 487561 ± 115724 arbitrary units, respectively; P = 0.804). Other outcomes (including 72-h AUC for CK-MB, C-reactive protein, need for defibrillation, time to extubation, length of ICU and hospital stay, and serious adverse events) were similar between the two groups. Conclusion In patients undergoing CABG on CPB, Intralipid did not limit myocardial IRI compared to placebo. Trial Registration ClinicalTrials.gov Identifier: NCT02807727 (registration date: 16 June 2016).
Since the discovery of the conditioning phenomenon in 1986 (whereby brief episodes of ischaemia reperfusion protect against a sustained ischaemic insult), thousands of preclinical studies have ...explored the benefits and signaling mechanisms of this cardioprotective strategy which aims to protect patients undergoing percutaneous coronary interventions (PCI), or cardiopulmonary bypass (CPB) surgery, against ischaemia reperfusion injury. A large number of proof of concept clinical trials have highlighted the benefits of conditioning to protect patients against ischaemia reperfusion injury, but none have yet translated to the clinical routine. The outcomes of the multicenter studies ERICCA, (1) RIP Heart (2) and CIRCUS (3) which involved larger number of patients (1 612, 1 385 and 970 respectively) were eagerly awaited, hoping that pharmacological conditioning with cyclosporine A, or remote ischaemic preconditioning,could soon become part of the clinical routine.
This study investigated supply chain collaboration, which is a topic of high interest in the field of supply chain management.Purpose: The purpose of this study was to investigate how collaborative ...relationships with international suppliers enhance supply chain efficiencies, ultimately improving the organisational performance of imported goods in the Fast Moving Consumer Goods (FMCG) industry.Methodology: A case study approach was adopted in this research, and an online survey was conducted with the international suppliers of NHM-SA (fictitious name). Data was collected from 91 international suppliers; however, only 50 suppliers provided usable data. A quantitative approach was used to investigate the relevance of supply chain collaboration in attaining supply chain operational efficiencies, which ultimately enhances organisational performance.Findings: The concept of supply chain collaboration is of importance in the FMCG industry but is often limited due to operational issues with constraints such as the partners’ lack of commitment to a collaborative relationship. The results provided empirical evidence, showing that cost optimisation, communication and information sharing have a positive effect on organisational performance. The study results also proved that supply chain collaboration have indirect positive impacts on organisational performance.Limitations: This study was limited to a single case study from the FMCG industry. Therefore, caution should be exercised when generalising the results. Participants provided responses based on their experiences and perceptions and may therefore not be factual.Practical implications: The study demonstrated the various methods in which organisations form collaborative supply chains with their partners. Such collaborative relationships enhanced operational efficiencies, joint planning and knowledge sharing, which led to the improved organisational performance of all partners involved in the collaboration.Originality / value: The study provided tangible evidence of the applicability of supply chain collaborative initiatives in the FMCG industry. The study thus provided important inputs on how such collaborative relationships with international suppliers can enhance supply chain efficiencies. The research, therefore, proved that higher organisational performance levels could be achieved through collaboration as opposed to operating in silos.
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