Senescence-Associated Secretory Phenotype as a Hinge Between Cardiovascular Diseases and Cancer

Banerjee, Priyanka; Kotla, Sivareddy; Velatooru, Loka Reddy; Abe, Rei; Davis, Elizabeth A.; Cooke, John P.; Schadler, Keri; Deswal, Anita; Herrmann, Joerg; Lin, Steven H.; Abe, Jun‐ichi; Le, Nhat-Tu

doi:10.3389/fcvm.2021.763930

Cited by 42 publications

(45 citation statements)

References 169 publications

(186 reference statements)

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“…Then, circulating monocytes invade the subendothelial space, absorb ox-LDL and convert into foam cells [ 96 ]. Both foam cells and ECs with the SASP release excess chemotactic proteins, including interleukin-1, tumour necrosis factor, and MCP-1, which lead to the recruitment of immune cells and the formation of atherosclerotic plaques [ 95 ]. ECs with the SASP can lead to thrombosis via the activation of PAI-1, a known marker of senescence [ 95 , 98 ].…”

Section: Senescence Of Endothelial Cellsmentioning

confidence: 99%

The multifaceted role of the SASP in atherosclerosis: from mechanisms to therapeutic opportunities

et al. 2022

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Background The global population of older individuals is growing, and ageing is a key risk factor for atherosclerotic cardiovascular diseases. Abnormal accumulation of senescent cells can cause potentially deleterious effects on the organism with age. As a vital marker of cellular senescence, the senescence-associated secretory phenotype (SASP) is a novel mechanism to link cellular senescence with atherosclerosis. Main body In this review, we concretely describe the characteristics of the SASP and its regulation mechanisms. Importantly, we provide novel perspectives on how the SASP can promote atherosclerosis. The SASP from different types of senescent cells have vital roles in atherosclerosis progression. As a significant mediator of the harmful effects of senescent cells, it can play a pro-atherogenic role by producing inflammation and immune dysfunction. Furthermore, the SASP can deliver senescence signals to the surrounding vascular cells, gradually contributing to the development of atherosclerosis. Finally, we focus on a variety of novel therapeutic strategies aimed to reduce the burden of atherosclerosis in elderly individuals by targeting senescent cells and inhibiting the regulatory mechanisms of the SASP. Conclusion This review systematically summarizes the multiple roles of the SASP in atherosclerosis and can contribute to the exploration of new therapeutic opportunities.

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Section: Senescence Of Endothelial Cellsmentioning

confidence: 99%

The multifaceted role of the SASP in atherosclerosis: from mechanisms to therapeutic opportunities

et al. 2022

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“…Oxidative stress is another mechanism associated with senescence and kidney damage [ 6 , 20 , 21 ]. Gene expression of redox-response-related factors, including Cat , Sod1, and Hmox-1 (which encodes for catalase, superoxide dismutase-1, and HO-1 protein, respectively) were analyzed.…”

Section: Resultsmentioning

confidence: 99%

“…Aging is related to telomere shortening due to replicative stress, and this can lead to cellular senescence [ 6 ]. This process is defined as an irreversible cell-cycle arrest (CCA), characterized by alterations in chromatin organization and gene expression, that induce profound phenotypic changes.…”

Section: Introductionmentioning

confidence: 99%

“…Oxidative stress plays a key role in the premature aging associated with CKD [ 21 ]. Reactive oxygen species (ROS) accumulation and redox imbalance can lead to tissue damage due to increased breakage of the DNA and consequent DDR, which leads to CDK inhibitor activation [ 6 , 20 ]. This state of cells involves the activation of one of the molecular pathways to remove ROS, the nuclear factor (erythroid-derived 2)-related factor 2/hemooxigenase-1 (NRF2/HO-1) axis [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

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Oxidative Stress and Cellular Senescence Are Involved in the Aging Kidney

et al. 2022

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Chronic kidney disease (CKD) can be considered as a clinical model for premature aging. However, non-invasive biomarkers to detect early kidney damage and the onset of a senescent phenotype are lacking. Most of the preclinical senescence studies in aging have been done in very old mice. Furthermore, the precise characterization and over-time development of age-related senescence in the kidney remain unclear. To address these limitations, the age-related activation of cellular senescence-associated mechanisms and their correlation with early structural changes in the kidney were investigated in 3- to 18-month-old C57BL6 mice. Inflammatory cell infiltration was observed by 12 months, whereas tubular damage and collagen accumulation occurred later. Early activation of cellular-senescence-associated mechanisms was found in 12-month-old mice, characterized by activation of the DNA-damage-response (DDR), mainly in tubular cells; activation of the antioxidant NRF2 pathway; and klotho downregulation. However, induction of tubular-cell-cycle-arrest (CCA) and overexpression of renal senescent-associated secretory phenotype (SASP) components was only found in 18-month-old mice. In aging mice, both inflammation and oxidative stress (marked by elevated lipid peroxidation and NRF2 inactivation) remained increased. These findings support the hypothesis that prolonged DDR and CCA, loss of nephroprotective factors (klotho), and dysfunctional redox regulatory mechanisms (NRF2/antioxidant defense) can be early drivers of age-related kidney-damage progression.

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“…They perpetuate a pro-inflammatory signaling loop and play a role in their own death, promoting the recruitment of immune cells, including Mφ which function collectively to clear the senescent cells ( Figure 4 ). However, the immune response declines with age (“immunosenescence”), and, as a result, the clearance of senescent cells is impaired [ 205 ].…”

Section: Macrophages Subsets and Cardiac Remodelingmentioning

confidence: 99%

Early Protective Role of Inflammation in Cardiac Remodeling and Heart Failure: Focus on TNFα and Resident Macrophages

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Nadaud

Balse

et al. 2022

Cells

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Cardiac hypertrophy, initiated by a variety of physiological or pathological stimuli (hemodynamic or hormonal stimulation or infarction), is a critical early adaptive compensatory response of the heart. The structural basis of the progression from compensated hypertrophy to pathological hypertrophy and heart failure is still largely unknown. In most cases, early activation of an inflammatory program reflects a reparative or protective response to other primary injurious processes. Later on, regardless of the underlying etiology, heart failure is always associated with both local and systemic activation of inflammatory signaling cascades. Cardiac macrophages are nodal regulators of inflammation. Resident macrophages mostly attenuate cardiac injury by secreting cytoprotective factors (cytokines, chemokines, and growth factors), scavenging damaged cells or mitochondrial debris, and regulating cardiac conduction, angiogenesis, lymphangiogenesis, and fibrosis. In contrast, excessive recruitment of monocyte-derived inflammatory macrophages largely contributes to the transition to heart failure. The current review examines the ambivalent role of inflammation (mainly TNFα-related) and cardiac macrophages (Mφ) in pathophysiologies from non-infarction origin, focusing on the protective signaling processes. Our objective is to illustrate how harnessing this knowledge could pave the way for innovative therapeutics in patients with heart failure.

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Senescence-Associated Secretory Phenotype as a Hinge Between Cardiovascular Diseases and Cancer

Cited by 42 publications

References 169 publications

The multifaceted role of the SASP in atherosclerosis: from mechanisms to therapeutic opportunities

The multifaceted role of the SASP in atherosclerosis: from mechanisms to therapeutic opportunities

Oxidative Stress and Cellular Senescence Are Involved in the Aging Kidney

Early Protective Role of Inflammation in Cardiac Remodeling and Heart Failure: Focus on TNFα and Resident Macrophages

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