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Combined effects of aging and inflammation on renin-angiotensin system mediate mitochondrial dysfunction and phenotypic changes in cardiomyopathies.

Burks TN, Marx R, Powell L, Rucker J, Bedja D, Heacock E, Smith BJ, Foster DB, Kass D, O'Rourke B, Walston JD, Abadir PM - Oncotarget (2015)

Bottom Line: We show molecular distinction in the combined effect of aging and inflammation as compared to each independently.Despite signaling pathway differences, the combined effect shared phenotypic similarities with aging including oxidative damage, fibrosis, and hypertrophy.Moreover, treatment with an AT(1)R blocker, losartan, selectively reversed the signaling changes and ameliorated adverse phenotypic effects in the combination of aging and inflammation as well as each independently.

View Article: PubMed Central - PubMed

Affiliation: Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine Baltimore, MD 21205, USA.

ABSTRACT
Although the effects of aging and inflammation on the health of the cardiac muscle are well documented, the combined effects of aging and chronic inflammation on cardiac muscle are largely unknown. The renin-angiotensin system (RAS) has been linked independently to both aging and inflammation, but is understudied in the context of their collective effect. Thus, we investigated localized cardiac angiotensin II type I and type II receptors (AT(1)R, AT(2)R), downstream effectors, and phenotypic outcomes using mouse models of the combination of aging and inflammation and compared it to a model of aging and a model of inflammation. We show molecular distinction in the combined effect of aging and inflammation as compared to each independently. The combination maintained an increased AT(1)R:AT(2)R and expression of Nox2 and exhibited the lowest activity of antioxidants. Despite signaling pathway differences, the combined effect shared phenotypic similarities with aging including oxidative damage, fibrosis, and hypertrophy. These phenotypic similarities have dubbed inflammatory conditions as premature aging, but they are, in fact, molecularly distinct. Moreover, treatment with an AT(1)R blocker, losartan, selectively reversed the signaling changes and ameliorated adverse phenotypic effects in the combination of aging and inflammation as well as each independently.

No MeSH data available.


Related in: MedlinePlus

Similarities and differences in the molecular mechanisms and phenotypic characteristics of aging, inflammation, and the combinationThere are shared and distinct characteristics of aging, inflammation and the combined effect of aging and inflammation in the pathogenesis of cardiomyopathy.
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Figure 8: Similarities and differences in the molecular mechanisms and phenotypic characteristics of aging, inflammation, and the combinationThere are shared and distinct characteristics of aging, inflammation and the combined effect of aging and inflammation in the pathogenesis of cardiomyopathy.

Mentions: Studies have shown an age-related cardiac hypertrophy and functional decline in older healthy individuals as well as in association with co-morbidities including frailty [9, 32]. Many studies have investigated the interface between RAS and mitochondrial health in the context of aging or inflammation but not the combination of both aging and inflammation. In this present study, we sought to determine the longitudinal effects of increased AT1R signaling in the pathological aging (combination of aging and inflammation) on cardiac muscle and mitochondria and how that compares to “normal” aging and inflammation independently (Figure 8). Moreover, conditions of chronic inflammation have been suggested to be premature or accelerated aging. However, our data suggests that aging and inflammation have distinct molecular mechanisms that in time will result in a similar phenotype such as cardiomyopathy.


Combined effects of aging and inflammation on renin-angiotensin system mediate mitochondrial dysfunction and phenotypic changes in cardiomyopathies.

Burks TN, Marx R, Powell L, Rucker J, Bedja D, Heacock E, Smith BJ, Foster DB, Kass D, O'Rourke B, Walston JD, Abadir PM - Oncotarget (2015)

Similarities and differences in the molecular mechanisms and phenotypic characteristics of aging, inflammation, and the combinationThere are shared and distinct characteristics of aging, inflammation and the combined effect of aging and inflammation in the pathogenesis of cardiomyopathy.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494917&req=5

Figure 8: Similarities and differences in the molecular mechanisms and phenotypic characteristics of aging, inflammation, and the combinationThere are shared and distinct characteristics of aging, inflammation and the combined effect of aging and inflammation in the pathogenesis of cardiomyopathy.
Mentions: Studies have shown an age-related cardiac hypertrophy and functional decline in older healthy individuals as well as in association with co-morbidities including frailty [9, 32]. Many studies have investigated the interface between RAS and mitochondrial health in the context of aging or inflammation but not the combination of both aging and inflammation. In this present study, we sought to determine the longitudinal effects of increased AT1R signaling in the pathological aging (combination of aging and inflammation) on cardiac muscle and mitochondria and how that compares to “normal” aging and inflammation independently (Figure 8). Moreover, conditions of chronic inflammation have been suggested to be premature or accelerated aging. However, our data suggests that aging and inflammation have distinct molecular mechanisms that in time will result in a similar phenotype such as cardiomyopathy.

Bottom Line: We show molecular distinction in the combined effect of aging and inflammation as compared to each independently.Despite signaling pathway differences, the combined effect shared phenotypic similarities with aging including oxidative damage, fibrosis, and hypertrophy.Moreover, treatment with an AT(1)R blocker, losartan, selectively reversed the signaling changes and ameliorated adverse phenotypic effects in the combination of aging and inflammation as well as each independently.

View Article: PubMed Central - PubMed

Affiliation: Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine Baltimore, MD 21205, USA.

ABSTRACT
Although the effects of aging and inflammation on the health of the cardiac muscle are well documented, the combined effects of aging and chronic inflammation on cardiac muscle are largely unknown. The renin-angiotensin system (RAS) has been linked independently to both aging and inflammation, but is understudied in the context of their collective effect. Thus, we investigated localized cardiac angiotensin II type I and type II receptors (AT(1)R, AT(2)R), downstream effectors, and phenotypic outcomes using mouse models of the combination of aging and inflammation and compared it to a model of aging and a model of inflammation. We show molecular distinction in the combined effect of aging and inflammation as compared to each independently. The combination maintained an increased AT(1)R:AT(2)R and expression of Nox2 and exhibited the lowest activity of antioxidants. Despite signaling pathway differences, the combined effect shared phenotypic similarities with aging including oxidative damage, fibrosis, and hypertrophy. These phenotypic similarities have dubbed inflammatory conditions as premature aging, but they are, in fact, molecularly distinct. Moreover, treatment with an AT(1)R blocker, losartan, selectively reversed the signaling changes and ameliorated adverse phenotypic effects in the combination of aging and inflammation as well as each independently.

No MeSH data available.


Related in: MedlinePlus