The involvement of Nox4 in fine particulate matter exposure-induced cardiac injury in mice

Abstract

-Epidemiological studies have confirmed that ambient fine particulate matter (PM 2.5 ) exposure is associated with cardiovascular disease (CVD). However, the underlying mechanisms in PM 2.5 exposure-induced heart injury are largely unknown. It has been acknowledged that NADPH oxidase (Nox) 4 plays a critical role in CVD development. To investigate the acute effects of PM 2.5 on the mouse heart and the role of Nox4 in PM 2.5 exposure-induced cardiac injury, C57BL/6J mice were instilled with saline or 1.5, 3.0, 6.0 mg/kg BW PM 2.5 suspension for two weeks (five days per week). The levels of malondialdehyde (MDA), super oxide dismutase (SOD), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β in heart supernatants were determined using related kits. The expression of Nox4, p67 phox , p47 phox and p22 phox in heart tissue was evaluated by immunofluorescence staining or Western blotting, respectively. Protein levels of p53, Bax, Bcl-2 and Caspase-3 in the heart were examined using immunohistochemical staining and Western blotting. TUNEL assay was used to measure myocardial apoptosis. PM 2.5 exposure leads to obvious cardiac injury. PM 2.5 exposure increases MDA level and iNOS activity, and decreases activity of SOD in heart supernatants of mice. High levels of TNF-α and IL-1β in heart supernatants of mice with PM 2.5 instillation were determined. Nox4 and Noxassociated subunits such as p67 phox , p47 phox and p22 phox expression levels were increased in heart tissue of mice after PM 2.5 exposure. Additionally, PM 2.5 exposure causes myocardial apoptosis in the mouse heart. This study suggested that Nox4 is involved in PM 2.5 exposure-induced cardiac injury in mice.

NLRP3 inflammasome activation is associated with PM2.5‐induced cardiac functional and pathological injury in mice

“…In addition, serious pathological changes were observed in the cardiac tissues of PM 2.5 ‐exposed mice. On one hand, a large number of inflammatory cells were discovered in PM 2.5 ‐exposed cardiac tissues, and similar pathological changes in cardiac tissues induced by PM 2.5 were also reported by a latest study . On the other hand, we found the upregulation of fibrosis area and the expression of fibrotic marker α‐SMA in the cardiac tissues of PM 2.5 ‐exposed mice compared with saline‐exposed mice, which were also confirmed by other reports …”

“…Haze had become a public health problem in some developing and developed countries. It was demonstrated that PM 2.5 was the culprit of haze weather in China . Increased evidences showed that PM 2.5 was involved in the development of CVDs .…”

“…A latest report showed that Al, Cr, Co, Ni, Se, Cd, Ba, Ti, and Pb in PM 2.5 could deposit in the prefrontal cortex of rats and regulate inflammation through NLRP3 inflammasome signal pathway . But in heart, only a report confirmed that IL‐1β protein, the key downstream factor of NLRP3 inflammasome activation, played an important role in PM 2.5 ‐induced cardiac injury . Thus, it was still unclear whether NLRP3 inflammasome activation was associated with PM 2.5 ‐induced cardiac injury.…”

“…Epidemiologic studies have confirmed that PM 2.5 exposure is closely related to the occurrence and development of cardiovascular diseases (CVDs) . Animal experiments have confirmed that short‐term exposure to ambient PM 2.5 could potentiate heart damage . According to report by World Health Organization, 17.3 million people died of CVDs every year, accounting for 30% of total deaths .…”

Activation of the mammalian target of rapamycin signaling pathway underlies a novel inhibitory role of ring finger protein 182 in ventricular remodeling after myocardial ischemia‐reperfusion injury

“…Another report also indicates that ischemia‐reperfusion has decreased the level of anti‐apoptotic protein Bcl‐2 and increased the level of pro‐apoptotic protein Bax . PM 2.5 exposure has been observed to elevate Bax, and caspase‐3 in cardiac tissues while reducing Bcl‐2 level, indicating its stimulation in myocardial cell apoptosis . Furthermore, mTOR plays a pivotal role in preventing cardiac dysfunction in pathological hypertrophy and crucially functions in protecting the heart from MIRI .…”