Table 1.
Potential therapeutic targets beyond airway patency
| Target | Study | Findings |
|---|---|---|
| Gut Dysbiosis | Moreno-Indias et al.40 | IH promotes Firmicutes and reduces Bacteroidetes in mice |
| Ganesh et al.36 | Cbutyricum butyricum and Hylon supplementation prevented IH-induced HTN in mice | |
| Moreno-Indias et al.41 | Normoxia does not reverse IH-induced gut dysbiosis in mice | |
| Ko et al.38 | Attenuated short-chain fatty acid producing bacteria in OSA | |
| Poroyko et al.39 | Increased Lachnospiraceae and Ruminococcaceae with reduced Lactobacillaceae following sleep fragmentation in mice | |
| Durgan et al.37 | Intermittent tracheal balloon inflation reduced butyrate-producing bacteria in mice; fecal transplant from these mice induced HTN in controls | |
| Autonomic Nervous System | Santisteban et al.48 | Spontaneously hypertensive and chronic Ang-II infusion rats had heightened sympathetically-mediated HTN and increased gut epithelial permeability |
| Narkiewicz et al.47 | 100% FiO2 reduced MSNA and MAP in OSA but not controls | |
| Narkiewicz et al.49 | Greater ventilatory, cardiac, and MAP responses to hypoxia in OSA vs. controls | |
| Narkiewicz et al.50 | Impaired sympathetic baroreflex function in normotensive OSA | |
| Narkiewicz et al.52 | Increased blood pressure variability and MSNA burst frequency, decreased heart rate variability in OSA | |
| Body/Visceral Fat Mass | Covassin et al.58 | Visceral fat mass correlated with elevations in blood pressure in healthy individuals |
| Romero-Corral et al.59 | Association between visceral, but not subcutaneous, fat gain and endothelial function in healthy individuals | |
| Ng et al.61 | 3mo of CPAP did not reduce visceral fat, body mass, nor carotid intima-media thickness in OSA | |
| Chin et al.62 | >6mo of CPAP reduced visceral fat and LDL with increased HDL in OSA | |
| Dixon et al.112 | Surgical and non-surgical weight loss reduced AHI | |
| Peppard et al.113 | 10% weight gain increased AHI 32% and risk of sleep-disordered >breathing six-fold; 10% weight loss reduced AHI 26% | |
| Grassi et al.114 | Obesity propagates MSNA and plasma [norepinephrine] in OSA | |
| Systemic Inflammation | Horvath et al.68 | Associations between C3a and OSA severity/C-reactive protein |
| Murphy et al.69 | IH reduced insulin sensitivity and induced pro-inflammatory phenotype in visceral adipocytes of mice | |
| Braley et al.74 | 4mo dimethyl fumarate supplementation reduced NFκB signaling in OSA | |
| Shamsuzzaman et al.9 | Increased C-reactive protein in CPAP-naïve OSA relative to controls | |
| Nitric Oxide Bioavailability | Varadharaj et al.78 | eNOS-derived NO is reduced in adipose microvessels of OSA; reversed with BH4 |
| Kato et al.7 | Acetylcholine- and flow mediated vasodilation is reduced in OSA | |
| Jelic et al.26 | Phosphorylated eNOS is reduced with OSA and reversed with CPAP | |
| Ozkan et al.27 | Exhaled NO positively correlated with nadir SpO2 and inversely correlated with oxidative stress in patients with OSA | |
| Ip et al.15 | Plasma [nitrate] and [nitrite] are reduced in OSA and increase following CPAP | |
| Gerbe et al.86 | Flow-mediated dilation is reduced with OSA and increased with Vitamin C infusion | |
| Bock et al.87 | Acute inorganic nitrate supplementation blunted increases in blood pressure and peripheral chemoreflex sensitivity in OSA | |
IH, intermittent hypoxia; HTN, hypertension; OSA, patients with obstructive sleep apnea; MSNA, muscle sympathetic nerve activity, MAP, mean arterial pressure; CPAP, continuous positive airway pressure; AHI, apnea-hypopnea index; eNOS, endothelial nitric oxide (NO) synthase; BH4, tetrahydrobiopterin.