Intermittent Hypoxia Alleviates β-Aminopropionitrile Monofumarate Induced Thoracic Aortic Dissection in C57BL/6 Mice.

Thoracic aortic dissection (TAD) has a high mortality rate. Intermittent hypoxia (IH) triggers both harmful and beneficial effects in numerous physiological systems. The effects of IH on TAD development were explored in a mouse model. β-Aminopropionitrile monofumarate (BAPN) was used to induce TAD in C57BL/6 mice. Three week old male mice were treated with 1 g/kg/day BAPN in drinking water for four weeks and simultaneously subjected to IH (n = 30) (21%-5% O2, 90 s/cycle, 10 h/day, IH + BAPN group) or normoxia (n = 30) (21% O2, 24 h/day, BAPN group). Human VSMCs (HUASMCs) exposed to IH (30 min, 5% O2)/re-oxygenation (30 min, 21% O2) cycles with a maximum of 60 min/cycle to detect the effect of IH on HIF-1α and LOX via HIF-1α-siRNA. It was found that BAPN administration significantly increased the lumen size and wall thickness of aortas compared with the normal group, but was significantly reversed by IH exposure. Additionally, IH exposure significantly increased the survival rate of BAPN induced TAD (70% vs. 40%). Furthermore, IH exposure reduced BAPN induced elastin breaks and apoptosis of vascular smooth muscle cells. IH exposure also reversed BAPN induced upregulation of inflammation and extracellular matrix (ECM) degradation. Real time polymerase chain reaction (RT-PCR) confirmed that IH inhibited inflammation and ECM degradation related genes interleukin (IL)-1β, IL-6, cathepsin S (Cat S), and matrix metalloproteinase 9 (MMP-9), but upregulated the ECM synthesis related genes lysyl oxidase (LOX) and collagen type I alpha2 (Col1a2) compared with the BAPN group. In vitro results suggest that IH promotes the expression of LOX via HIF-1α. The results suggest that IH alleviates BAPN induced TAD in C57BL/6 mice.

Yang YY ，Li LY ，Jiao XL ，Jia LX ，Zhang XP ，Wang YL ，Yang S ，Li J ，Du J ，Wei YX ，Qin YW ... -  《-》

Moderate aerobic exercise prevents matrix degradation and death in a mouse model of aortic dissection and aneurysm.

Aicher BO ，Zhang J ，Muratoglu SC ，Galisteo R ，Arai AL ，Gray VL ，Lal BK ，Strickland DK ，Ucuzian AA ... -  《-》

Blocking Interleukin-1 Beta Reduces the Evolution of Thoracic Aortic Dissection in a Rodent Model.

Thoracic aortic dissection (TAD) is associated with matrix changes, biochemical changes, and inflammatory markers like interleukin-1 beta (IL-1β). However, the exact mechanism remains unknown. This study aimed to investigate the role of IL-1β, matrix metalloproteinase (MMP)-2, MMP-9, smooth muscle cell apoptosis, and elastic fibre fracture in the development of TAD in a rat model. The TAD rat model was induced by β-aminopropionitrile (BAPN). TAD was investigated in 112 male Sprague-Dawley rats, which were equally divided into four groups of 28 rats (Control, BAPN, BAPN + IL-1β, and BAPN + IL-1β antibody). Systolic blood pressure, survival, and the development of TAD were measured after six weeks. Expression of IL-1β, MMP-2, and MMP-9 was measured by Western blot. Apoptosis, aortic elastin concentration, and biomechanical characteristics were measured by the TdT mediated dUTP nick end labelling assay, Victoria blue staining, and in vitro testing. During six weeks, the mortality was 0% (0/28) in the control group, 53.6% (15/28) in the BAPN group (p < .001 compared with the control group), 75.0% (21/28) in the BAPN + IL-1β group (p = .007 compared with the BAPN group), and 35.7% (10/28) in the BAPN + IL-1β antibody group (p = .023 compared with BAPN group and p < .001 compared with the BAPN + IL-1β group). IL-1β treatment deteriorates BAPN induced mortality and aneurysm expansion, which were attenuated by anti-IL-1β treatment. In BAPN + IL-1β group, stress and strain parameters were decreased by 13.5%-53.5% and elastin content was decreased by 14%, and IL-1β, MMP-2, and MMP-9 were expressed higher by 117%, 108%, and 75% when compared with the rats in the BAPN group. Contrarily, in the BAPN + IL-1β antibody group, the above changes could be completely (strain, elastin content, and expression of MMP-2) or partly (elasticity modulus, stress, and expression of MMP-9) blocked by anti-IL-1β treatment. IL-1β plays a critical role in TAD formation by altering the expression of MMP-2 and MMP-9, degrading the aortic wall matrix, causing elastic fibre rupture, and changing the stress or strain of the aortic wall. Anti-IL-1β reduces the later effects and could be one of the molecular targets for prognosis and drug treatment of TAD in the future.

Guo LL ，Wu MT ，Zhang LW ，Chu YX ，Tian P ，Jing ZP ，Li JS ，Sun YD ，Yeung KK ，Zhang L ... -  《-》

Effects of Extracellular Matrix Softening on Vascular Smooth Muscle Cell Dysfunction.

Shao Y ，Li G ，Huang S ，Li Z ，Qiao B ，Chen D ，Li Y ，Liu H ，Du J ，Li P ... -  《-》

Low Zinc Alleviates the Progression of Thoracic Aortic Dissection by Inhibiting Inflammation.

Zhu L ，An P ，Zhao W ，Xia Y ，Qi J ，Luo J ，Luo Y ... -  《Nutrients》