Heart failure (HF) with preserved (HFpEF) and reduced (HFrEF) ejection fraction may be driven by different pathophysiologies. We explored novel biomarkers, associations with clinical characteristics, Show more
Heart failure (HF) with preserved (HFpEF) and reduced (HFrEF) ejection fraction may be driven by different pathophysiologies. We explored novel biomarkers, associations with clinical characteristics, discrimination between LVEF categories and associations with outcomes. In HFpEF(n=76) and HFrEF(n=36), 19 plasma biomarkers were measured including seven novel research assays for ANGPT2, BMP10, DKK3, FABP3, FGF23, IGFBP7 and MYBPC3. HFpEF patients were older (73 vs 63 years), more often female (50% vs 14%). All seven novel biomarkers except FABP3 tended to be higher in HFrEF vs HFpEF and associated with worse NYHA class and lower eGFR in both LVEF categories. MYBPC3 and FGF23 (higher in HFrEF) discriminated best between LVEF categories (AUC 85.8 and 80.0 respectively). In HFpEF, higher ANGPT2 was associated with worse right (TAPSE:β=-1.03;p=0.04) and left ventricular function (LV-GLS; β=1.29;p=0.03) and left atrial strain (LA-GLS:β=5.03;p<0.001) whereas higher IGFBP7 and MYBPC3 with diastolic dysfunction (E/e´:β=4.09;p=0.02 and β=1.36;p=0.01 respectively). All biomarkers except DKK3 were positively associated with the outcome (HFpEF:all-cause death, HF-hospitalization;HFrEF: all-cause death, LVAD or heart transplantation). Specifically (ANGPT2 (HR 1.45[95% CI 1.00-2.13]) more strongly in HFpEF and IGFBP7 (2.51[0.95-6.64]) more strongly in HFrEF (MYBPC3 (1.62[0.99-2.64]). Among seven novel biomarker assays, higher MYBPC3 (reflecting muscle injury and myopathy) and FGF23 (endothelial dysfunction, oxidative stress) distinguished HFrEF from HFpEF. Higher MYBPC3 was most prognostic in HFrEF while higher ANGPT2 and IGFBP7 (endothelial dysfunction and oxidative stress) in HFpEF. These hypothesis-generating findings support primary cardiomyocyte injury as a driver of HFrEF and systemic inflammation and oxidative stress as a driver of HFpEF. ClinicalTrials.gov NCT00774709. Show less
Batten disease (BD) is the most common form of a group of disorders called neuronal ceroid lipofuscinosis, which are caused by a CLN3 gene mutation. A variety of pathogenic lysosomal storage disorder Show more
Batten disease (BD) is the most common form of a group of disorders called neuronal ceroid lipofuscinosis, which are caused by a CLN3 gene mutation. A variety of pathogenic lysosomal storage disorder mechanisms have been suggested such as oxidative stress, endoplasmic reticulum (ER) stress, and altered protein trafficking. Resveratrol, a stilbenoid found in red grape skin, is a potent antioxidant chemical. Recent studies have suggested that resveratrol may have a curative effect in many neurodegenerative diseases. Therefore, we investigated the activities of resveratrol at the levels of oxidative and ER stress and apoptosis factors using normal and BD lymphoblast cells. We report that the BD lymphoblast cells contained low-levels of superoxide dismutase-1 (SOD-1) due to the long-term stress of reactive oxygen species. However, when we treated the cells with resveratrol, SOD-1 increased to levels observed in normal cells. Furthermore, we investigated the expression of glucose-regulated protein 78 as an ER stress marker. BD cells underwent ER stress, but resveratrol treatment resolved the ER stress in a dose-dependent manner. We further demonstrated that the levels of apoptosis markers such as apoptosis induce factor, cytochrome c, and cleavage of poly (ADP)-ribose polymerase decreased following resveratrol treatment. Thus, we propose that resveratrol may have beneficial effects in patients with BD. Show less