Insight into the Role of the PI3K/Akt Pathway in Ischemic Injury and Post-Infarct Left Ventricular Remodeling in Normal and Diabetic Heart

Walkowski, Bartosz; Kleibert, Marcin; Majka, Miłosz; Wojciechowska, Małgorzata

doi:10.3390/cells11091553

Cited by 52 publications

(21 citation statements)

References 328 publications

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“…Still, they returned to baseline values after LM22A-4, in keeping with the idea that chronically elevated Akt activity underpins adverse remodeling and loss of inotropy. 26 Thus, TrkB agonism arrests CHF progression via BDNF-evoked improvement of myocardial cell survival/function and preserved cardiac sympathetic innervation and vascularity.…”

Section: Resultsmentioning

confidence: 99%

β3AR-Dependent Brain-Derived Neurotrophic Factor (BDNF) Generation Limits Chronic Postischemic Heart Failure

Cannavò

Jun

Rengo

et al. 2023

Circulation Research

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Background: Loss of brain-derived neurotrophic factor (BDNF)/TrkB (tropomyosin kinase receptor B) signaling accounts for brain and cardiac disorders. In neurons, β-adrenergic receptor stimulation enhances local BDNF expression. It is unclear if this occurs in a pathophysiological relevant manner in the heart, especially in the β-adrenergic receptor-desensitized postischemic myocardium. Nor is it fully understood whether and how TrkB agonists counter chronic postischemic left ventricle (LV) decompensation, a significant unmet clinical milestone. Methods: We conducted in vitro studies using neonatal rat and adult murine cardiomyocytes, SH-SY5Y neuronal cells, and umbilical vein endothelial cells. We assessed myocardial ischemia (MI) impact in WT, β3AR KO, or myocyte-selective BDNF KO (myoBDNF KO) mice in vivo (via coronary ligation [MI]) or in isolated hearts with global ischemia-reperfusion (I/R). Results: In WT hearts, BDNF levels rose early after MI (<24 hours), plummeting at 4 weeks when LV dysfunction, adrenergic denervation, and impaired angiogenesis ensued. The TrkB agonist, LM22A-4, countered all these adverse effects. Compared with WT, isolated myoBDNF KO hearts displayed worse infarct size/LV dysfunction after I/R injury and modest benefits from LM22A-4. In vitro, LM22A-4 promoted neurite outgrowth and neovascularization, boosting myocyte function, effects reproduced by 7,8-dihydroxyflavone, a chemically unrelated TrkB agonist. Superfusing myocytes with the β3AR-agonist, BRL-37344, increased myocyte BDNF content, while β3AR signaling underscored BDNF generation/protection in post-MI hearts. Accordingly, the β1AR blocker, metoprolol, via upregulated β3ARs, improved chronic post-MI LV dysfunction, enriching the myocardium with BDNF. Last, BRL-37344-imparted benefits were nearly abolished in isolated I/R injured myoBDNF KO hearts. Conclusions: BDNF loss underscores chronic postischemic heart failure. TrkB agonists can improve ischemic LV dysfunction via replenished myocardial BDNF content. Direct cardiac β3AR stimulation, or β-blockers (via upregulated β3AR), is another BDNF-based means to fend off chronic postischemic heart failure.

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Section: Resultsmentioning

confidence: 99%

β3AR-Dependent Brain-Derived Neurotrophic Factor (BDNF) Generation Limits Chronic Postischemic Heart Failure

Cannavò

Jun

Rengo

et al. 2023

Circulation Research

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“…Hence, cardio‐protective bioactive compounds may target this signaling cascade to promote NO generation and vasodilation. [ 50 ]…”

Section: Biological Targets Of Microalgae Peptides For Promoting Card...mentioning

confidence: 99%

“…Hence, cardio-protective bioactive compounds may target this signaling cascade to promote NO generation and vasodilation. [50] Recent studies have continued to report microalgae bioactive peptides with blood pressure-reducing potentials through PI3K/AKT/eNOS signaling cascades. For example, Carrizzo and colleagues [51] isolated a novel decameric peptide from microalga Spirulina platensis with the potential to increase the vascular generation of NO as a vasoprotectant in resistance vessels of mice.…”

Section: Endothelial Nitric Oxide Synthase (Enos) As a Target For Pro...mentioning

confidence: 99%

Big Things, Small Packages: An Update on Microalgae as Sustainable Sources of Nutraceutical Peptides for Promoting Cardiovascular Health

et al. 2023

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In 2017, a review of microalgae protein‐derived bioactive peptides relevant in cardiovascular disease (CVD) management was published. Given the rapid evolution of the field, an update is needed to illumininate recent developments and proffer future suggestions. In this review, the scientific literature (2018–2022) is mined for that purpose and the relevant properties of the identified peptides related to CVD are discussed. The challenges and prospects for microalgae peptides are similarly discussed. Since 2018, several publications have independently confirmed the potential to produce microalgae protein‐derived nutraceutical peptides. Peptides that reduce hypertension (by inhibiting angiotensin converting enzyme and endothelial nitric oxide synthase), modulate dyslipidemia and have antioxidant and anti‐inflammatory properties have been reported, and characterized. Taken together, future research and development investments in nutraceutical peptides from microalgae proteins need to focus on the challenges of large‐scale biomass production, improvement in techniques for protein extraction, peptide release and processing, and the need for clinical trials to validate the claimed health benefits as well as formulation of various consumer products with the novel bioactive ingredients.

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“…PI3K/Akt pathway promotes cell survival through the inhibition of apoptosis. Moreover, in the pathogeny of MI, the PI3K-AKT pathway has an anti-apoptotic effect [ 149 ]. This effect would be explained by translocation of phospho-AKT (pAKT) with secondary modification of cytochrome c oxidase (CcO) activity [ 138 ].…”

Section: Putative Future Cellular Therapiesmentioning

confidence: 99%

Dynamic Involvement of Telocytes in Modulating Multiple Signaling Pathways in Cardiac Cytoarchitecture

Cucu

Nicolescu

Busnatu

et al. 2022

IJMS

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Cardiac interstitium is a complex and dynamic environment, vital for normal cardiac structure and function. Telocytes are active cellular players in regulating main events that feature myocardial homeostasis and orchestrating its involvement in heart pathology. Despite the great amount of data suggesting (microscopically, proteomically, genetically, etc.) the implications of telocytes in the different physiological and reparatory/regenerative processes of the heart, understanding their involvement in realizing the heart’s mature cytoarchitecture is still at its dawn. Our scrutiny of the recent literature gave clearer insights into the implications of telocytes in the WNT signaling pathway, but also TGFB and PI3K/AKT pathways that, inter alia, conduct cardiomyocytes differentiation, maturation and final integration into heart adult architecture. These data also strengthen evidence for telocytes as promising candidates for cellular therapies in various heart pathologies.

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Insight into the Role of the PI3K/Akt Pathway in Ischemic Injury and Post-Infarct Left Ventricular Remodeling in Normal and Diabetic Heart

Cited by 52 publications

References 328 publications

β3AR-Dependent Brain-Derived Neurotrophic Factor (BDNF) Generation Limits Chronic Postischemic Heart Failure

β3AR-Dependent Brain-Derived Neurotrophic Factor (BDNF) Generation Limits Chronic Postischemic Heart Failure

Big Things, Small Packages: An Update on Microalgae as Sustainable Sources of Nutraceutical Peptides for Promoting Cardiovascular Health

Dynamic Involvement of Telocytes in Modulating Multiple Signaling Pathways in Cardiac Cytoarchitecture

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