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Acute and subchronic exposure to air particulate matter induces expression of angiotensin and bradykinin-related genes in the lungs and heart: Angiotensin-II type-I receptor as a molecular target of particulate matter exposure.

Aztatzi-Aguilar OG, Uribe-Ramírez M, Arias-Montaño JA, Barbier O, De Vizcaya-Ruiz A - Part Fibre Toxicol (2015)

Bottom Line: The PM fractions induced the expression of RAAS and KKS elements in the lungs and heart in a time-dependent manner.The AT1R lung protein showed a time-dependent change in subcellular distribution.In addition, the presence of AT1R in the heart was accompanied by a decrease in HO-1, which was concomitant with the induction of Acta1 and Col3a1 and the increment of IL-6.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Avenida Instituto Politécnico Nacional, 2508, México D. F, CP. 07360, Mexico. gammaztatzi@gmail.com.

ABSTRACT

Background: Particulate matter (PM) adverse effects on health include lung and heart damage. The renin-angiotensin-aldosterone (RAAS) and kallikrein-kinin (KKS) endocrine systems are involved in the pathophysiology of cardiovascular diseases and have been found to impact lung diseases. The aim of the present study was to evaluate whether PM exposure regulates elements of RAAS and KKS.

Methods: Sprague-Dawley rats were acutely (3 days) and subchronically (8 weeks) exposed to coarse (CP), fine (FP) or ultrafine (UFP) particulates using a particulate concentrator, and a control group exposed to filtered air (FA). We evaluated the mRNA of the RAAS components At1, At2r and Ace, and of the KKS components B1r, B2r and Klk-1 by RT-PCR in the lungs and heart. The ACE and AT1R protein were evaluated by Western blot, as were HO-1 and γGCSc as indicators of the antioxidant response and IL-6 levels as an inflammation marker. We performed a binding assay to determinate AT1R density in the lung, also the subcellular AT1R distribution in the lungs was evaluated. Finally, we performed a histological analysis of intramyocardial coronary arteries and the expression of markers of heart gene reprogramming (Acta1 and Col3a1).

Results: The PM fractions induced the expression of RAAS and KKS elements in the lungs and heart in a time-dependent manner. CP exposure induced Ace mRNA expression and regulated its protein in the lungs. Acute and subchronic exposure to FP and UFP induced the expression of At1r in the lungs and heart. All PM fractions increased the AT1R protein in a size-dependent manner in the lungs and heart after subchronic exposure. The AT1R lung protein showed a time-dependent change in subcellular distribution. In addition, the presence of AT1R in the heart was accompanied by a decrease in HO-1, which was concomitant with the induction of Acta1 and Col3a1 and the increment of IL-6. Moreover, exposure to all PM fractions increased coronary artery wall thickness.

Conclusion: We demonstrate that exposure to PM induces the expression of RAAS and KKS elements, including AT1R, which was the main target in the lungs and the heart.

No MeSH data available.


Related in: MedlinePlus

Acute, but not subchronic, exposure to particle matter increases IL-6 in lungs. Animals were exposed to coarse (CP), fine (FP) and ultrafine particulate (UFP), or filtered air (FA). The protein interleukine-6 (IL-6) levels after a) acute (3 days, 5 h/day) and b) subchronic exposure (8 weeks, 5 h/day, 4 days/week), are shown as arbitrary units (AU). Scatter dot plot shows the value of the median. * indicates significant differences among groups (n = 4 per group, p < 0.05)
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Fig5: Acute, but not subchronic, exposure to particle matter increases IL-6 in lungs. Animals were exposed to coarse (CP), fine (FP) and ultrafine particulate (UFP), or filtered air (FA). The protein interleukine-6 (IL-6) levels after a) acute (3 days, 5 h/day) and b) subchronic exposure (8 weeks, 5 h/day, 4 days/week), are shown as arbitrary units (AU). Scatter dot plot shows the value of the median. * indicates significant differences among groups (n = 4 per group, p < 0.05)

Mentions: Pleiotropic cytokine IL-6 is involved in the acute phase of inflammation and accelerates coagulation induced by PM exposure in vivo [5]. In addition, in endothelium cells, IL-6 induced the expression of AT1R [24]. We observed a statistically significant increase in lung IL-6 protein from the acute exposure to the three PM fractions (Fig. 5a); on the other hand, in the subchronic exposure a down regulation in the three PM groups below the levels observed in the FA group was observed (Fig. 5b). Our results indicate the induction of lung IL-6 as a marker of the acute phase of the inflammation process. IL-6 could be involved in the up-regulation of AT1R in lung acute PM exposure. In contrast, in the subchronic exposure a lack of induction of lung IL-6 protein was observed and AT1R expression was increased. If a molecular communication process takes place between IL-6 and AT1R it only happens acutely, but not subchronically, yet this hypothesis needs to be confirmed.


Acute and subchronic exposure to air particulate matter induces expression of angiotensin and bradykinin-related genes in the lungs and heart: Angiotensin-II type-I receptor as a molecular target of particulate matter exposure.

Aztatzi-Aguilar OG, Uribe-Ramírez M, Arias-Montaño JA, Barbier O, De Vizcaya-Ruiz A - Part Fibre Toxicol (2015)

Acute, but not subchronic, exposure to particle matter increases IL-6 in lungs. Animals were exposed to coarse (CP), fine (FP) and ultrafine particulate (UFP), or filtered air (FA). The protein interleukine-6 (IL-6) levels after a) acute (3 days, 5 h/day) and b) subchronic exposure (8 weeks, 5 h/day, 4 days/week), are shown as arbitrary units (AU). Scatter dot plot shows the value of the median. * indicates significant differences among groups (n = 4 per group, p < 0.05)
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4482198&req=5

Fig5: Acute, but not subchronic, exposure to particle matter increases IL-6 in lungs. Animals were exposed to coarse (CP), fine (FP) and ultrafine particulate (UFP), or filtered air (FA). The protein interleukine-6 (IL-6) levels after a) acute (3 days, 5 h/day) and b) subchronic exposure (8 weeks, 5 h/day, 4 days/week), are shown as arbitrary units (AU). Scatter dot plot shows the value of the median. * indicates significant differences among groups (n = 4 per group, p < 0.05)
Mentions: Pleiotropic cytokine IL-6 is involved in the acute phase of inflammation and accelerates coagulation induced by PM exposure in vivo [5]. In addition, in endothelium cells, IL-6 induced the expression of AT1R [24]. We observed a statistically significant increase in lung IL-6 protein from the acute exposure to the three PM fractions (Fig. 5a); on the other hand, in the subchronic exposure a down regulation in the three PM groups below the levels observed in the FA group was observed (Fig. 5b). Our results indicate the induction of lung IL-6 as a marker of the acute phase of the inflammation process. IL-6 could be involved in the up-regulation of AT1R in lung acute PM exposure. In contrast, in the subchronic exposure a lack of induction of lung IL-6 protein was observed and AT1R expression was increased. If a molecular communication process takes place between IL-6 and AT1R it only happens acutely, but not subchronically, yet this hypothesis needs to be confirmed.

Bottom Line: The PM fractions induced the expression of RAAS and KKS elements in the lungs and heart in a time-dependent manner.The AT1R lung protein showed a time-dependent change in subcellular distribution.In addition, the presence of AT1R in the heart was accompanied by a decrease in HO-1, which was concomitant with the induction of Acta1 and Col3a1 and the increment of IL-6.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Avenida Instituto Politécnico Nacional, 2508, México D. F, CP. 07360, Mexico. gammaztatzi@gmail.com.

ABSTRACT

Background: Particulate matter (PM) adverse effects on health include lung and heart damage. The renin-angiotensin-aldosterone (RAAS) and kallikrein-kinin (KKS) endocrine systems are involved in the pathophysiology of cardiovascular diseases and have been found to impact lung diseases. The aim of the present study was to evaluate whether PM exposure regulates elements of RAAS and KKS.

Methods: Sprague-Dawley rats were acutely (3 days) and subchronically (8 weeks) exposed to coarse (CP), fine (FP) or ultrafine (UFP) particulates using a particulate concentrator, and a control group exposed to filtered air (FA). We evaluated the mRNA of the RAAS components At1, At2r and Ace, and of the KKS components B1r, B2r and Klk-1 by RT-PCR in the lungs and heart. The ACE and AT1R protein were evaluated by Western blot, as were HO-1 and γGCSc as indicators of the antioxidant response and IL-6 levels as an inflammation marker. We performed a binding assay to determinate AT1R density in the lung, also the subcellular AT1R distribution in the lungs was evaluated. Finally, we performed a histological analysis of intramyocardial coronary arteries and the expression of markers of heart gene reprogramming (Acta1 and Col3a1).

Results: The PM fractions induced the expression of RAAS and KKS elements in the lungs and heart in a time-dependent manner. CP exposure induced Ace mRNA expression and regulated its protein in the lungs. Acute and subchronic exposure to FP and UFP induced the expression of At1r in the lungs and heart. All PM fractions increased the AT1R protein in a size-dependent manner in the lungs and heart after subchronic exposure. The AT1R lung protein showed a time-dependent change in subcellular distribution. In addition, the presence of AT1R in the heart was accompanied by a decrease in HO-1, which was concomitant with the induction of Acta1 and Col3a1 and the increment of IL-6. Moreover, exposure to all PM fractions increased coronary artery wall thickness.

Conclusion: We demonstrate that exposure to PM induces the expression of RAAS and KKS elements, including AT1R, which was the main target in the lungs and the heart.

No MeSH data available.


Related in: MedlinePlus