Long-term cardiovascular complications following sepsis: is senescence the missing link?

Merdji, Hamid; Schini‐Kerth, Valérie B.; Meziani, Ferhat; Toti, Florence

doi:10.1186/s13613-021-00937-y

Cited by 35 publications

(25 citation statements)

References 112 publications

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“…SIPS not only plays a role in the arrest of cell cycle and cell propagation in replicating tissues 67 , but also impairs the functionality of organs with scarce residual replicative capacity, as it is the heart. SIPS is considered a novel mechanism in the heart remodelling after acute myocardial infarction 27 , 68 , cancer therapy-induced cardiotoxicity 28 and long-term cardiovascular complications following sepsis 12 . Maejima et al reported that murine neonatal CMs that undergo SIPS have common features of replicative-senescence, including upregulation of cell-cycle regulatory inhibitors, expression of SA-β-gal, and the attenuation of telomerase activity 23 .…”

Section: Discussionmentioning

confidence: 99%

“…Cardiomyocytes (CMs) enduring exogenous cellular insult may develop a stress-induced premature senescence (SIPS) phenotype, which recapitulates many cellular and molecular features as those undergoing natural aging process 10 , 11 . SIPS has emerged as possible link between long-term consequences of some pathological conditions such as sepsis 12 or anthracycline cardiotoxicity 13 and cardiovascular complications 14 , 15 . Nowadays, cellular mechanisms behind such unexplained cardiac abnormalities regardless of age, are not completely understood.…”

Section: Introductionmentioning

confidence: 99%

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Stress-induced premature senescence is associated with a prolonged QT interval and recapitulates features of cardiac aging

Lazzarini¹,

Lodrini²,

Arici³

et al. 2022

Theranostics

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Rationale: Aging in the heart is a gradual process, involving continuous changes in cardiovascular cells, including cardiomyocytes (CMs), namely cellular senescence. These changes finally lead to adverse organ remodeling and resulting in heart failure. This study exploits CMs from human induced pluripotent stem cells (iCMs) as a tool to model and characterize mechanisms involved in aging. Methods and Results: Human somatic cells were reprogrammed into human induced pluripotent stem cells and subsequently differentiated in iCMs. A senescent-like phenotype (SenCMs) was induced by short exposure (3 hours) to doxorubicin (Dox) at the sub-lethal concentration of 0.2 µM. Dox treatment induced expression of cyclin-dependent kinase inhibitors p21 and p16, and increased positivity to senescence-associated beta-galactosidase when compared to untreated iCMs. SenCMs showed increased oxidative stress, alteration in mitochondrial morphology and depolarized mitochondrial membrane potential, which resulted in decreased ATP production. Functionally, when compared to iCMs, SenCMs showed, prolonged multicellular QTc and single cell APD, with increased APD variability and delayed afterdepolarizations (DADs) incidence, two well-known arrhythmogenic indexes. These effects were largely ascribable to augmented late sodium current (I NaL ) and reduced delayed rectifier potassium current (Ikr). Moreover sarcoplasmic reticulum (SR) Ca 2+ content was reduced because of downregulated SERCA2 and increased RyR2-mediated Ca 2+ leak. Electrical and intracellular Ca 2+ alterations were mostly justified by increased CaMKII activity in SenCMs. Finally, SenCMs phenotype was furtherly confirmed by analyzing physiological aging in CMs isolated from old mice in comparison to young ones. Conclusions: Overall, we showed that SenCMs recapitulate the phenotype of aged primary CMs in terms of senescence markers, electrical and Ca 2+ handling properties and metabolic features. Thus, Dox-induced SenCMs can be considered a novel in vitro platform to study aging mechanisms and to envision cardiac specific anti-aging approach in humans.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Stress-induced premature senescence is associated with a prolonged QT interval and recapitulates features of cardiac aging

Lazzarini¹,

Lodrini²,

Arici³

et al. 2022

Theranostics

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“…The current study also revealed that CVD and DM patients had more bacteremia than other recruited patients. Studies have shown that bacteremia can lead to sepsis, which carries an increased risk of cardiovascular complications, such as myocardial infarction, acute heart failure, or stroke [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Bacterial Infections among Patients with Chronic Diseases at a Tertiary Care Hospital in Saudi Arabia

et al. 2022

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Infections caused by multi-drug-resistant bacteria in patients with chronic diseases have been associated with high mortality and morbidity. While few reports have evaluated bacterial infections in multiple chronic disease patients, the focus of the current study was to investigate the prevalence of bacterial infections and the susceptibility profiles of causative strains among various groups of patients suffering from chronic diseases. Microbiological reports of patients suffering from cancer, diabetes mellitus, cardiovascular diseases, kidney diseases, and skin burns were retrospectively collected from a tertiary hospital in Saudi Arabia. Approximately 54.2% of recruited patients were males, and positive urine was the most prevalent specimen associated with kidney disease patients (25%). Escherichia coli isolates were predominant among cardiovascular, kidney, and cancer patients. Staphylococcus aureus was commonly detected in diabetics and those with burns. Although resistance patterns varied based on the type of specimens and underlying diseases, Escherichia coli showed limited resistance to colistin, carbapenems, and tigecycline, while S. aureus demonstrated susceptibility to ciprofloxacin, gentamicin, and rifampin. These observations are crucial for clinicians and policymakers to ensure effective treatment plans and improve outcomes in these patients with comorbidity.

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“…However, effort to reduce sepsisrelated morbidity and mortality have mostly concentrated on increasing short-term survival, with little emphasis placed on late morbidity and disease trajectories after hospital discharge. As the number of sepsis survivors increases, assessing the risk of late complications becomes critically important (8)(9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Long-term risk and predictors of cerebrovascular events following sepsis hospitalization: A systematic review and meta-analysis

et al. 2022

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BackgroundLong-term risk and predictors of cerebrovascular events following sepsis hospitalization have not been clearly elucidated. We aim to determine the association between surviving sepsis hospitalization and cerebrovascular complications in adult sepsis survivors.MethodWe searched MEDLINE, Embase, Scopus, Web of Sciences, Cochrane library, and Google scholar for studies published from the inception of each database until 31 August 2022.ResultsOf 8,601 screened citations, 12 observational studies involving 829,506 participants were analyzed. Surviving sepsis hospitalization was associated with a significantly higher ischemic stroke [adjusted hazard ratio (aHR) 1.45 (95% CI, 1.23–1.71), I2 = 96], and hemorrhagic stroke [aHR 2.22 (95% CI, 1.11–4.42), I2 = 96] at maximum follow-up compared to non-sepsis hospital or population control. The increased risk was robust to several sensitivity analyses. Factors that were significantly associated with increased hazards of stroke were: advanced age, male gender, diabetes mellitus, hypertension, coronary artery disease, chronic heart failure, chronic kidney disease, chronic obstruction pulmonary disease, and new-onset atrial fibrillation. Only diabetes mellites [aHR 1.80 (95% CI, 1.12–2.91)], hypertension [aHR 2.2 (95% CI, 2.03–2.52)], coronary artery disease [HR 1.64 (95% CI, 1.49–1.80)], and new-onset atrial fibrillation [aHR 1.80 (95% CI, 1.42–2.28)], were associated with > 50% increase in hazards.ConclusionOur findings showed a significant association between sepsis and a subsequent risk of cerebrovascular events. The risk of cerebrovascular events can be predicated by patient and sepsis-related baseline variables. New therapeutic strategies are needed for the high-risk patients.

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Long-term cardiovascular complications following sepsis: is senescence the missing link?

Cited by 35 publications

References 112 publications

Stress-induced premature senescence is associated with a prolonged QT interval and recapitulates features of cardiac aging

Stress-induced premature senescence is associated with a prolonged QT interval and recapitulates features of cardiac aging

Bacterial Infections among Patients with Chronic Diseases at a Tertiary Care Hospital in Saudi Arabia

Long-term risk and predictors of cerebrovascular events following sepsis hospitalization: A systematic review and meta-analysis

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