Cardiovascular Inflammaging: Mechanisms and Translational Aspects

Arellano, Maria Luisa Barcena de; Aslam, Muhammad; Pozdniakova, Sofya; Norman, Kristina; Ladilov, Yury

doi:10.3390/cells11061010

Cited by 33 publications

(41 citation statements)

References 164 publications

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“…eNOS uncoupling occurs when the availability of the critical cofactor tetrahydrobiopterin (BH4) is inadequate, leading eNOS to produce superoxide anion instead of NO [ 109 ]. In aged rats’ arterioles, reduced levels of BH4 were accompanied by impaired endothelium-dependent vasodilation [ 123 ]. Furthermore, in estrogen-deficient postmenopausal women, reduced vascular BH4 seems to be an important contributor to arterial stiffening, related in part to reduced endothelial-dependent vasodilatory tone [ 124 ].…”

Section: Aging-related Changes In Skeletal Muscle and Cardiovascular ...mentioning

confidence: 99%

Effect of Physical Activity/Exercise on Oxidative Stress and Inflammation in Muscle and Vascular Aging

Assar

Álvarez‐Bustos

Sosa

et al. 2022

IJMS

133

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Functional status is considered the main determinant of healthy aging. Impairment in skeletal muscle and the cardiovascular system, two interrelated systems, results in compromised functional status in aging. Increased oxidative stress and inflammation in older subjects constitute the background for skeletal muscle and cardiovascular system alterations. Aged skeletal muscle mass and strength impairment is related to anabolic resistance, mitochondrial dysfunction, increased oxidative stress and inflammation as well as a reduced antioxidant response and myokine profile. Arterial stiffness and endothelial function stand out as the main cardiovascular alterations related to aging, where increased systemic and vascular oxidative stress and inflammation play a key role. Physical activity and exercise training arise as modifiable determinants of functional outcomes in older persons. Exercise enhances antioxidant response, decreases age-related oxidative stress and pro-inflammatory signals, and promotes the activation of anabolic and mitochondrial biogenesis pathways in skeletal muscle. Additionally, exercise improves endothelial function and arterial stiffness by reducing inflammatory and oxidative damage signaling in vascular tissue together with an increase in antioxidant enzymes and nitric oxide availability, globally promoting functional performance and healthy aging. This review focuses on the role of oxidative stress and inflammation in aged musculoskeletal and vascular systems and how physical activity/exercise influences functional status in the elderly.

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Section: Aging-related Changes In Skeletal Muscle and Cardiovascular ...mentioning

confidence: 99%

Effect of Physical Activity/Exercise on Oxidative Stress and Inflammation in Muscle and Vascular Aging

Assar

Álvarez‐Bustos

Sosa

et al. 2022

IJMS

133

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“…On the one hand, myocardial FFAR3 activated by SCFAs, such as propionic acid, upregulates several pro-inflammatory (IL-1β, IL-6, activated p38 MAPK) [ 32 ] and pro-fibrotic (e.g., TGFβ [ 26 ]) factors, which is highly likely to lead to exacerbated adverse remodeling in the presence of a cardiac insult, such as myocardial ischemia/infarction or pressure overload/severe hypertension ( Figure 5 ). Furthermore, TGFβ, but also inflammation and fibrosis in general, have been implicated in cardiac aging [ 33 , 34 , 35 ]. Thus, FFAR3 signaling may also promote cardiac aging and RGS4, and by opposing FFAR3 effects, may have anti-aging properties in the heart.…”

Section: Discussionmentioning

confidence: 99%

Regulator of G-Protein Signaling-4 Attenuates Cardiac Adverse Remodeling and Neuronal Norepinephrine Release-Promoting Free Fatty Acid Receptor FFAR3 Signaling

Carbone

Borges

Suster

et al. 2022

IJMS

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Propionic acid is a cell nutrient but also a stimulus for cellular signaling. Free fatty acid receptor (FFAR)-3, also known as GPR41, is a Gi/o protein-coupled receptor (GPCR) that mediates some of the propionate’s actions in cells, such as inflammation, fibrosis, and increased firing/norepinephrine release from peripheral sympathetic neurons. The regulator of G-protein Signaling (RGS)-4 inactivates (terminates) both Gi/o- and Gq-protein signaling and, in the heart, protects against atrial fibrillation via calcium signaling attenuation. RGS4 activity is stimulated by β-adrenergic receptors (ARs) via protein kinase A (PKA)-dependent phosphorylation. Herein, we examined whether RGS4 modulates cardiac FFAR3 signaling/function. We report that RGS4 is essential for dampening of FFAR3 signaling in H9c2 cardiomyocytes, since siRNA-mediated RGS4 depletion significantly enhanced propionate-dependent cAMP lowering, Gi/o activation, p38 MAPK activation, pro-inflammatory interleukin (IL)-1β and IL-6 production, and pro-fibrotic transforming growth factor (TGF)-β synthesis. Additionally, catecholamine pretreatment blocked propionic acid/FFAR3 signaling via PKA-dependent activation of RGS4 in H9c2 cardiomyocytes. Finally, RGS4 opposes FFAR3-dependent norepinephrine release from sympathetic-like neurons (differentiated Neuro-2a cells) co-cultured with H9c2 cardiomyocytes, thereby preserving the functional βAR number of the cardiomyocytes. In conclusion, RGS4 appears essential for propionate/FFAR3 signaling attenuation in both cardiomyocytes and sympathetic neurons, leading to cardioprotection against inflammation/adverse remodeling and to sympatholysis, respectively.

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“…At the same time, the activation step, triggered by pathogen-activated molecular patterns (PAMPs) and DAMPs, promotes NLRP3 inflammasome installation and caspase-1-mediated IL-1 β and IL-18 release and pyroptosis [ 23 ]. The importance of NLRP3 inflammasome in inflamm-ageing is supported by the evidence that its inhibition is associated with an enhanced health span and reduced age-dependent degenerative changes; its activity and enhancement, instead, is related to an increased risk of age-related disorders, such as atherosclerosis and neurodegenerative diseases [ 42 ].…”

Section: Cellular Senescence and Inflamm-ageingmentioning

confidence: 99%

Endothelial Dysfunction and Chronic Inflammation: The Cornerstones of Vascular Alterations in Age-Related Diseases

Pacinella

Ciaccio

Tuttolomondo

2022

IJMS

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Vascular diseases of the elderly are a topic of enormous interest in clinical practice, as they have great epidemiological significance and lead to ever-increasing healthcare expenditures. The mechanisms underlying these pathologies have been increasingly characterized over the years. It has emerged that endothelial dysfunction and chronic inflammation play a diriment role among the most relevant pathophysiological mechanisms. As one can easily imagine, various processes occur during aging, and several pathways undergo irreversible alterations that can promote the decline and aberrations that trigger the diseases above. Endothelial dysfunction and aging of circulating and resident cells are the main characteristics of the aged organism; they represent the framework within which an enormous array of molecular abnormalities occur and contribute to accelerating and perpetuating the decline of organs and tissues. Recognizing and detailing each of these dysfunctional pathways is helpful for therapeutic purposes, as it allows one to hypothesize the possibility of tailoring interventions to the damaged mechanism and hypothetically limiting the cascade of events that drive the onset of these diseases. With this paper, we have reviewed the scientific literature, analysing the pathophysiological basis of the vascular diseases of the elderly and pausing to reflect on attempts to interrupt the vicious cycle that connotes the diseases of aging, laying the groundwork for therapeutic reasoning and expanding the field of scientific research by moving from a solid foundation.

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Cardiovascular Inflammaging: Mechanisms and Translational Aspects

Cited by 33 publications

References 164 publications

Effect of Physical Activity/Exercise on Oxidative Stress and Inflammation in Muscle and Vascular Aging

Effect of Physical Activity/Exercise on Oxidative Stress and Inflammation in Muscle and Vascular Aging

Regulator of G-Protein Signaling-4 Attenuates Cardiac Adverse Remodeling and Neuronal Norepinephrine Release-Promoting Free Fatty Acid Receptor FFAR3 Signaling

Endothelial Dysfunction and Chronic Inflammation: The Cornerstones of Vascular Alterations in Age-Related Diseases

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