Inflammaging: mechanisms and role in the cardiac and vasculature

Ajoolabady, Amir; Praticò, Domenico; Vinciguerra, Manlio; Lip, Gregory Y.H.; Franceschi, Claudio; Ren, Jun

doi:10.1016/j.tem.2023.03.005

Cited by 17 publications

(9 citation statements)

References 112 publications

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“…Hypertension refers to a clinical syndrome characterized by an increase in body circulatory arterial blood pressure (systolic/ Frontiers in Pharmacology frontiersin.org diastolic blood pressure), accompanied by functional or organic damage of the heart, brain, kidney, and other organs. Pathological studies found that the staining of the liver in hypertensive rats was shallow and that the structure was disordered, with nuclear consolidation, obvious edema, and fat degeneration (Ajoolabady et al, 2023). Simultaneously, the glomerulus shrinkage became smaller, the cystic cavity expanded, the renal tubular arrangement was disordered, and the lumen was narrowed (Harrison et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Investigation of the molecular mechanism of Smilax glabra Roxb. in treating hypertension based on proteomics and bioinformatics

Yang,

Qian,

Yang

et al. 2024

Front. Pharmacol.

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BackgroundSmilax glabra Roxb. (named tufuling in Chinese, SGR) has both medicinal and edible value. SGR has obvious pharmacological activity, especially in anti-inflammation and treating immune system diseases. This study investigated differential protein expression and its relationship with immune infiltration in hypertension treated with SGR using proteomics and bioinformatics.MethodsN-Nitro L-arginine methyl ester (L-NAME) was used to replicate the hypertension model, with SGR administered by gavage for 4 weeks, and the systolic and diastolic blood pressure in each group of rats was measured using the tail-cuff method every 7 days. Furthermore, enzyme-linked immunosorbent assay (ELISA) was used to determine the serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) expressions in each group, followed by the detection of protein expression in rat liver samples using the tandem mass tag (TMT) technique. Additionally, hub targets were output using Cytoscape 3.9.1 software, and ALDH2 expression in the liver and serum in each group of rats was detected by ELISA. Moreover, R4.3.0 software was used to evaluate the relationship between acetaldehyde dehydrogenase 2 (ALDH2) and immune cells, and ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) was performed to identify the components of SGR. Furthermore, the association between components of SGR and ALDH2 was analyzed with molecular docking and LigPlot1.4.5 software.ResultsCompared with the model group (L-NAME), SGR at high and medium doses reduced systolic and diastolic blood pressure while reducing TC, TG, and LDL-C levels and increasing HDL-C levels in hypertensive rats (p < 0.05). Moreover, 92 differentially expressed proteins (DEPs) were identified using TMT. These DEPs participated in peroxisome functioning, fatty acid degradation, and other signaling pathways, with ALDH2 being the core target and correlated with various immune cells. In addition, 18 components were determined in SGR, with 8 compounds binding to ALDH2. Molecular docking was performed to confirm that SGR played a role in hypertension based on the combined action of multiple components.ConclusionIn conclusion, SGR has an antihypertensive effect on L-NAME-induced hypertension, with ALDH2 as its hub target. SGR may regulate neutrophil, regulatory T cell, and other cells’ infiltration by targeting ALDH2, thereby contributing to the treatment of hypertension.

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Section: Discussionmentioning

confidence: 99%

Investigation of the molecular mechanism of Smilax glabra Roxb. in treating hypertension based on proteomics and bioinformatics

Yang,

Qian,

Yang

et al. 2024

Front. Pharmacol.

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“…The persistent lowgrade inflammation stimulates the dysregulation of vascular smooth muscle cells, promoting their proliferation and migration. This dysregulation contributes to arterial stiffening, a hallmark of vascular aging, and plays a role in the development of hypertension and other cardiovascular pathologies (13,30,32). Activation of immune cells, particularly monocytes, macrophages, and T lymphocytes, within the vascular microenvironment further promotes oxidative stress by increasing the production of ROS.…”

Section: Inflammaging and Cardiovascular Diseasesmentioning

confidence: 99%

“…In the complex interplay between aging and cardiovascular health, inflammaging emerges as a central player, orchestrating molecular and cellular events that significantly impact the development and progression of cardiovascular diseases ( 6 , 12 , 13 ). A multidimensional dynamic interaction, involving cytokines, inflammasomes, and senescent cells, actively triggering a prolonged pro-inflammatory environment ( Figure 1 ), characterize age-associated immune changes ( 7 ).…”

Section: Inflammaging and Cardiovascular Diseasesmentioning

confidence: 99%

Inflammaging, immunosenescence, and cardiovascular aging: insights into long COVID implications

Müller,

Di Benedetto

2024

Front. Cardiovasc. Med.

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Aging leads to physiological changes, including inflammaging—a chronic low-grade inflammatory state with significant implications for various physiological systems, particularly for cardiovascular health. Concurrently, immunosenescence—the age-related decline in immune function, exacerbates vulnerabilities to cardiovascular pathologies in older individuals. Examining the dynamic connections between immunosenescence, inflammation, and cardiovascular aging, this mini-review aims to disentangle some of these interactions for a better understanding of their complex interplay. In the context of cardiovascular aging, the chronic inflammatory state associated with inflammaging compromises vascular integrity and function, contributing to atherosclerosis, endothelial dysfunction, arterial stiffening, and hypertension. The aging immune system's decline amplifies oxidative stress, fostering an environment conducive to atherosclerotic plaque formation. Noteworthy inflammatory markers, such as the high-sensitivity C-reactive protein, interleukin-6, interleukin-1β, interleukin-18, and tumor necrosis factor-alpha emerge as key players in cardiovascular aging, triggering inflammatory signaling pathways and intensifying inflammaging and immunosenescence. In this review we aim to explore the molecular and cellular mechanisms underlying inflammaging and immunosenescence, shedding light on their nuanced contributions to cardiovascular diseases. Furthermore, we explore the reciprocal relationship between immunosenescence and inflammaging, revealing a self-reinforcing cycle that intensifies cardiovascular risks. This understanding opens avenues for potential therapeutic targets to break this cycle and mitigate cardiovascular dysfunction in aging individuals. Furthermore, we address the implications of Long COVID, introducing an additional layer of complexity to the relationship between aging, immunosenescence, inflammaging, and cardiovascular health. Our review aims to stimulate continued exploration and advance our understanding within the realm of aging and cardiovascular health.

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“…Notably, cardiac aging is associated with vascular aging characterized by impaired endothelium-dependent vasodilation and defective vessel repair capacity, and these features are associated with severe atherosclerosis and microvascular dysfunction [ 87 – 89 ]. Indeed, modern concepts suggest that cardiac aging can be declined as cardiovascular-inflammaging, since inflammaging in vascular and cardiac tissues is associated with the emergence of pathological states such as atherosclerosis and hypertension [ 90 – 92 ].…”

Section: Ans Imbalance and Inflammaging In The Heart: Focus On Heart ...mentioning

confidence: 99%

Autonomic nervous system imbalance during aging contributes to impair endogenous anti-inflammaging strategies

Giunta,

Xia,

Pelliccioni

et al. 2023

GeroScience

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Inflammaging refers to the age-related low grade, sterile, chronic, systemic, and long-lasting subclinical, proinflammatory status, currently recognized as the main risk factor for development and progression of the most common age-related diseases (ARDs). Extensive investigations were focused on a plethora of proinflammatory stimuli that can fuel inflammaging, underestimating and partly neglecting important endogenous anti-inflammaging mechanisms that could play a crucial role in such age-related proinflammatory state. Studies on autonomic nervous system (ANS) functions during aging highlighted an imbalance toward an overactive sympathetic nervous system (SNS) tone, promoting proinflammatory conditions, and a diminished parasympathetic nervous system (PNS) activity, playing anti-inflammatory effects mediated by the so called cholinergic anti-inflammatory pathway (CAP). At the molecular level, CAP is characterized by signals communicated via the vagus nerve (with the possible involvement of the splenic nerves) through acetylcholine release to downregulate the inflammatory actions of macrophages, key players of inflammaging. Notably, decreased vagal function and increased burden of activated/senescent macrophages (macrophaging) probably precede the development of several age-related risk factors and diseases, while increased vagal function and reduced macrophaging could be associated with relevant reduction of risk profiles. Hypothalamic–pituitary–adrenal axis (HPA axis) is another pathway related to ANS promoting some anti-inflammatory response mainly through increased cortisol levels. In this perspective review, we highlighted that CAP and HPA, representing broadly “anti-inflammaging” mechanisms, have a reduced efficacy and lose effectiveness in aged people, a phenomenon that could contribute to fuel inflammaging. In this framework, strategies aimed to re-balance PNS/SNS activities could be explored to modulate systemic inflammaging especially at an early subclinical stage, thus increasing the chances to reach the extreme limit of human lifespan in healthy status.

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Inflammaging: mechanisms and role in the cardiac and vasculature

Cited by 17 publications

References 112 publications

Investigation of the molecular mechanism of Smilax glabra Roxb. in treating hypertension based on proteomics and bioinformatics

Investigation of the molecular mechanism of Smilax glabra Roxb. in treating hypertension based on proteomics and bioinformatics

Inflammaging, immunosenescence, and cardiovascular aging: insights into long COVID implications

Autonomic nervous system imbalance during aging contributes to impair endogenous anti-inflammaging strategies

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