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Intermittent hypoxia (IH) is the predominant pathophysiological disturbance in obstructive sleep apnea (OSA), known to be independently associated with cardiovascular diseases. However, the effect of IH on cardiac fibrosis and molecular events involved in this process are unclear. Here, we tested IH in angiotensin II (Ang II)-induced cardiac fibrosis and signaling linked to fibroblast activation. IH triggered cardiac fibrosis and aggravated Ang II-induced cardiac dysfunction in mice. Plasma thrombospondin-1 (TSP1) content was upregulated in both IH-exposed mice and OSA patients. Moreover, both and results showed IH-induced cardiac fibroblast activation and increased TSP1 expression in cardiac fibroblasts. Mechanistically, phosphorylation of STAT3 at Tyr705 mediated the IH-induced TSP1 expression and fibroblast activation. Finally, STAT3 inhibitor S3I-201 or AAV9 carrying a periostin promoter driving the expression of shRNA targeting Stat3 significantly attenuated the synergistic effects of IH and Ang II on cardiac fibrosis in mice. This work suggests a potential therapeutic strategy for OSA-related fibrotic heart disease.
This article was published in the following journal.
Cardiac fibrosis (CF) is regulated by multiple factors, including transforming growth factor β1 (TGFβ1) and non-coding RNAs. Thrombospondin 1 (TSP1) is a physiologic regulator of TGFβ activation. H...
Age-related macular degeneration is a progressive ocular disease that is the leading cause of vision loss among elderly. AMD usually is divided into two types: wet and dry AMD, which is linked with in...
In neonates, catecholamine (CA) secretion from adrenal medullary chromaffin cells (AMC) is an important mechanism for maintaining homeostasis during hypoxia. Nearly 90% of premature infants experience...
Intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), is prevalent in older adults and associated with inflammation. We previously showed that IH induces renal fibrosis and cardiomyo...
Due to the high prevalence of both obstructive sleep apnea syndrome (OSA) and end-stage renal disease (ESRD), the co-existence of both conditions in peritoneal dialysis is demonstrated. Because OSA-in...
This is a randomized control pilot study to assess the effect of intermittent hypoxia therapy on functional capacity vs conventional care in old patients with functional impairment admitte...
This project seeks to investigate the effects of a single acute intermittent hypoxia (AIH) session on respiratory and non-respiratory motor function and EMG (electromyography) activity on ...
Specific aim To examine the effect of catecholamines on the modulation of intermittent hypoxia induced TNF- in human monocytes from both healthy subjects and OSA patients (2). To map th...
This study will utilize short duration and mild levels of reduced oxygen (hypoxia) to induce spinal plasticity while evaluating the appropriate timing schedule for this intervention, as we...
The objective of this study is to examine the effects of mild acute intermittent hypoxia (AIH) in combination with an anti-inflammatory drug (i.e. prednisolone) on motor performance in per...
Dioxygenase enzymes that specifically hydroxylate a PROLINE residue on the HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT. They are OXYGEN-dependent enzymes that play an important role in mediating cellular adaptive responses to HYPOXIA.
A signal transducer and activator of transcription that mediates cellular responses to INTERLEUKIN-6 family members. STAT3 is constitutively activated in a variety of TUMORS and is a major downstream transducer for the CYTOKINE RECEPTOR GP130.
Cell surface receptors for obesity factor (LEPTIN), a hormone secreted by the WHITE ADIPOCYTES. Upon leptin-receptor interaction, the signal is mediated through the JAK2/STAT3 pathway to regulate food intake, energy balance and fat storage.
A protein that plays a fundamental role in the Vitamin D mediated transport of calcium in reptiles, amphibians, birds and mammals. It is found in the intestine, kidneys, egg shell gland, brain, and possibly other organs. Its molecular weight is species dependent.
Excessive periodic leg movements during sleep that cause micro-arousals and interfere with the maintenance of sleep. This condition induces a state of relative sleep deprivation which manifests as excessive daytime hypersomnolence. The movements are characterized by repetitive contractions of the tibialis anterior muscle, extension of the toe, and intermittent flexion of the hip, knee and ankle. (Adams et al., Principles of Neurology, 6th ed, p387)
Sleep disorders disrupt sleep during the night, or cause sleepiness during the day, caused by physiological or psychological factors. The common ones include snoring and sleep apnea, insomnia, parasomnias, sleep paralysis, restless legs syndrome, circa...
Cardiovascular disease (CVD)
Acute Coronary Syndromes (ACS) Blood Cardiovascular Dialysis Hypertension Stent Stroke Vascular Cardiovascular disease (CVD) includes all the diseases of the heart and circulation including coronary heart disease (angina...
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells. In vertebrates, it is composed of blo...