PM2.5 induced cardiac hypertrophy via CREB/GSK3b/SOS1 pathway and metabolomics alterations

Abstract

The particle matter with diameter less 2.5μm (PM2.5) easier to adsorb toxic substance, and interfere with pulmonary gas exchange. In this study, cardioprotective effects of low molecular weight (LMW) fucoidan in cardiac hypertrophy subjects induced by PM2.5 exposure was conducted by measuring QT interval, Blood pressure, cardiac structure, metabolites and proteins expression in different organs. After PM2.5 exposure, increase in blood pressure, abnormal cardiac function (Prolongation of Action Potential Duration and QT Interval), and structral remodeling (cardiac hypertrophy and fibrosis) were recorded. Fucoidan supplement in consecutive 28 days can reduce the damage to myocardial injury caused by PM2.5. Clearance effect of fucoidan in serum, heart, kidney, lung and liver was found due to organic and inorganic compounds reduced SOS1, CREB, GSK3b, and GRB2 protein level were changed under PM2.5 exposure. Whereas, only CREB level was reduced after fucoidan treatment. Metabolic alteration was also determined that PM2.5 severely damage cardiac tissue and compromise its function. After treatment with fucoidan, the cardiac function was significantly recovered. Our finding demonstrated that LMW could enhance the cardiac status of mice with PM2.5 exposures by rescued QT interval prolongation, action potential and cardiac hypertrophy, and cardiac fibrosis decline.

Exposure to Particulate Matter in the Broiler House Causes Dyslipidemia and Exacerbates It by Damaging Lung Tissue in Broilers

“…After cessation of PM exposure, hyperlipidemia downregulated Fas gene expression and upregulated Hmgcs2 expression with negative feedback decreasing the hyperlipidemia to the normal level. These results indicated that PM 2.5 in poultry houses could cause hepatic dyslipidemia in broilers, which is also supported by published papers [ 26 , 29 ].…”

“…Many studies have reported that PM 2.5 exposure can induce distinct inflammatory signaling in the lung and liver [ 24 ]. Tumor necrosis factor (TNF)-α associated hepatic dyslipidemia [ 25 ] and cardiac hypertrophy [ 26 ] cause liver fibrosis [ 27 , 28 ] and elevate the risk of oxidative stress-driven nonalcoholic fatty liver disease [ 29 ]. These cases suggested that PM 2.5 not only dwells in the lungs but also is likely to cross the air–blood barrier and adversely affect the liver through the blood circulation system.…”

Cardiovascular adaptations to particle inhalation exposure: molecular mechanisms of the toxicology

“…Fine PM exposures can also lead to sustained detrimental effects in the heart by altering the transcription factor profile. One example of this has been shown previously in a cohort of PM 2.5 -exposed mice (89). Cardiac remodeling through hypertrophy, QT interval prolongation, and fibrosis were correlated with elevated cAMP response element-binding protein (CREB) as well as SOS Ras/Rac guanine nucleotide exchange factor 1 (SOS1) and glycogen synthase kinase-3␤ (GSK3␤) expression.…”

Left Ventricular Hypertrophy: Roles of Mitochondria CYP1B1 and Melatonergic Pathways in Co-Ordinating Wider Pathophysiology

“…A wide array of studies using different experimental paradigms show pathological cardiac hypertrophy to be significantly attenuated by p38MAPK pathway inhibition [11,12,13]. p38MAPK pathway activity leads to the downstream activation of cyclic adenosine 3′,5′-monophosphate (cAMP)-response element binding protein (CREB), with CREB interacting with DNA and regulating a plethora of gene transcriptions strongly associated with LVH [14]. Brain-derived neurotrophic factor (BDNF) is also increased in LVH [15] and can contribute to LVH pathophysiology via two-way activation interactions with CREB, with increased BDNF also being induced by p38MAPK [16].…”