As the age of the basic population boosts, so does the need for precision treatments for age-related heart health decrease. Heart failure is an increasing worldwide cardiovascular epidemic driven by aging and chronic inflammation. However, despite research study efforts to establish cardiac arrest drivers and comprehend the pathophysiology of age-related cardiac arrest, methods for prevention or treating the origin remain elusive.1 Cells become senescent when they reach a specific age that indicates them to stop growing and dividing. Senescent cells secrete numerous proteins associated with cellular aging and pathological processes, including the metabolic protein insulin-like development factor-binding protein-7 (IGFBP7). Utilizing proteomics, researchers identified IGFBP7 as a prospective biomarker for cardiac arrest, and in 2017, the American Heart Association recognized this protein as an important biomarker for cardiac arrest diagnosis and medical diagnosis based upon medical information. Its involvement in the underlying pathology of heart failure is of interest to clinicians and scientists alike.2-4 “The big question everybody asks is: Is it an onlooker, or is it a factor?” discussed Peter Liu, the chief clinical officer and vice president of research at the University of Ottawa Heart Institute, who was among the first scientists to determine IGFBP7s role in heart failure diagnostics, and whose research team released new findings answering this concern in Nature Cardiovascular Research.4 In the study, Lius team discovered that IGFBP7 is overexpressed in the heart and blood of patients with chronic cardiac arrest and in a cardiac arrest mouse design, promoting heart cell senescence. They discovered that neutralizing or downregulating IGFBP7 acts in opposition to the cardiac renovation that drives cardiac arrest. Diving deeper into the molecular paths, the scientists found that upregulated IGFBP7 promotes cardiac renovation and senescence by reducing the anti-senescence factor FOXO3a, avoiding DNA repair and reactive oxygen species detoxification.This work develops on previous clinical human research, including a big mate study where researchers linked IGFBP7 pathways to different stages of immune system regulation that impact inflammation, which has ramifications for both heart failure and senescence in human patients.2 “We did the molecular work finding that if you actually genetically eliminate [IGFBP7], it can in fact improve the heart function, decrease the fibrosis, decrease the hypertrophy, decrease the cell death, decrease the aging signals,” said Liu. “Its really directly adding to all these effects.” We are cautiously positive that this may be a therapeutic target. – Peter Liu, University of Ottawa Heart Institute”We are very carefully optimistic that this may be a therapeutic target,” said Liu. Future avenues for studying the function of this protein in heart failure will consist of analyzing therapeutic methods such as blocking IGFBP7 with antibodies or downregulating its expression with RNA-based therapeutics. “The nice thing is that by blocking this, by silencing [IGFBP7], you can in fact see substantial benefit in decreasing the seriousness of heart failure,” said Gary Lopaschuk, adjunct teacher and AHFMR researcher at the University of Alberta, who was not associated with the research study. “Its not simply a biomarker, it really is a targetable intervention.”Additionally, Lius research study suggests that selectively targeting IGFBP7-regulated senescence pathways may have restorative potential for dealing with aging-related pathologies beyond cardiac arrest, as IGFBP7 concentrations are predictive of both renal and heart occasions among people with type 2 diabetes and high cardiovascular threat.5 “We know that procedures [that] speed up aging will lead to diabetes, and diabetes can accelerate aging, and we tend to treat them independently,” discussed Liu. “In fact, there could be extremely much synergistic links in between the 2 … If we really have tools to deal with aging and diabetes, it may really have crossover benefits and may help to recognize more particles like IGFBP7.”ReferencesH. Li et al., “Targeting age-related paths in heart failure,” Circ Res, 126( 4 ):533 -51, 2020. V. Bracun et al., “Insulin-like development element binding protein 7 (IGFBP7), a link in between heart failure and senescence,” ESC Heart Fail, 9( 6 ):4167 -76, 2022. A. Bayes-Genis et al., “Omics phenotyping in cardiac arrest: the next frontier,” Eur Heart J, 41( 36 ):3477 -84, 2020. L. Zhang et al., “Insulin-like growth factor-binding protein-7 (IGFBP7) links senescence to heart failure,” Nat Cardiovasc Res, 1:1195 -1214, 2022. J.L. Januzzi et al., “Insulin-like growth factor binding protein 7 forecasts kidney and cardiovascular outcomes in the Canagliflozin Cardiovascular Assessment Study,” Diabetes Care, 44( 1 ):210 -16, 2021.
Utilizing proteomics, researchers determined IGFBP7 as a possible biomarker for heart failure, and in 2017, the American Heart Association recognized this protein as an important biomarker for heart failure diagnosis and medical diagnosis based on clinical data. They found that reducing the effects of or downregulating IGFBP7 acts in opposition to the heart improvement that drives heart failure. V. Bracun et al., “Insulin-like development aspect binding protein 7 (IGFBP7), a link between heart failure and senescence,” ESC Heart Fail, 9( 6 ):4167 -76, 2022. A. Bayes-Genis et al., “Omics phenotyping in heart failure: the next frontier,” Eur Heart J, 41( 36 ):3477 -84, 2020. L. Zhang et al., “Insulin-like growth factor-binding protein-7 (IGFBP7) links senescence to heart failure,” Nat Cardiovasc Res, 1:1195 -1214, 2022.
