Post-ischemic cardioprotective potential of exogenous ubiquitin in myocardial remodeling late after ischemia/reperfusion injury

Dalal, Suman; Shook, Paige; Singh, Mahipal; Singh, Krishna

doi:10.1016/j.lfs.2022.121216

Cited by 4 publications

(4 citation statements)

References 71 publications

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“…Conserved small molecular protein ubiquitin regulates protein turnover via the ubiquitin-proteasome system. Post-ischemic ubiquitin treatment attenuates cardiac dysfunction, myocardial fibrosis, apoptosis, hypertrophy, and serum cytokine/chemokine levels ( Dalal et al, 2023 ), which suggests ubiquitin has a protective role in cardiac remodeling. Conversely, an endogenous E3 ubiquitin ligase ring-finger protein four knockdown induces extensive interstitial fibrosis after MI ( Qiu et al, 2020 ).…”

Section: Interventions For Cardiac Fibrosismentioning

confidence: 99%

Post-myocardial infarction fibrosis: Pathophysiology, examination, and intervention

Yin

Pan

et al. 2023

Front. Pharmacol.

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Cardiac fibrosis plays an indispensable role in cardiac tissue homeostasis and repair after myocardial infarction (MI). The cardiac fibroblast-to-myofibroblast differentiation and extracellular matrix collagen deposition are the hallmarks of cardiac fibrosis, which are modulated by multiple signaling pathways and various types of cells in time-dependent manners. Our understanding of the development of cardiac fibrosis after MI has evolved in basic and clinical researches, and the regulation of fibrotic remodeling may facilitate novel diagnostic and therapeutic strategies, and finally improve outcomes. Here, we aim to elaborate pathophysiology, examination and intervention of cardiac fibrosis after MI.

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Section: Interventions For Cardiac Fibrosismentioning

confidence: 99%

Post-myocardial infarction fibrosis: Pathophysiology, examination, and intervention

Yin

Pan

et al. 2023

Front. Pharmacol.

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“…Likewise, ex vivo UB treatment decreased infarct size and improved the functional recovery of the heart following global I/R [ 18 ]. Long-term beneficial effects of eUB are demonstrated by the observation of improved heart function and decreased myocardial fibrosis, apoptosis, and hypertrophy in UB-treated hearts 28 days post-I/R in mice [ 96 ]. Thus, UB treatment significantly improves cardiac function and reduces adverse cardiac remodeling parameters in mouse models of chronic β-AR stimulation and I/R injury.…”

Section: Ubiquitin and The Heartmentioning

confidence: 99%

“…eUB has been suggested to have immunomodulatory effects. It has been shown to reduce inflammation and tissue injury in multiple models including endotoxemia, blunt polytrauma with lung injury, severe trauma, controlled cortical impact injury, lung I/R injury, and myocardial I/R injury [ 15 , 16 , 17 , 96 , 97 , 98 , 99 ]. In a swine endotoxemia model, UB treatment reduced mortality and prevented the development of pulmonary failure.…”

Section: Exogenous Ub and Immune Modulationmentioning

confidence: 99%

“…UB treatment was also associated with improved heart function 28 days post-I/R injury in mice. Circulating levels of IL-6, G-CSF, and IL-2 were lower in UB-treated I/R group vs. I/R [ 96 ]. In human PBMNCs, which can include monocytes that are precursors to macrophages, eUB inhibited TNF-α expression and secretion in response to LPS [ 14 ].…”

Section: Exogenous Ub and Immune Modulationmentioning

confidence: 99%

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Macrophages in the Inflammatory Phase following Myocardial Infarction: Role of Exogenous Ubiquitin

Shook,

Singh,

Singh

2023

Biology

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Cardiovascular disease (CVD) is one of the leading causes of death worldwide. One of the most common implications of CVD is myocardial infarction (MI). Following MI, the repair of the infarcted heart occurs through three distinct, yet overlapping phases of inflammation, proliferation, and maturation. Macrophages are essential to the resolution of the inflammatory phase due to their role in phagocytosis and efferocytosis. However, excessive and long-term macrophage accumulation at the area of injury and dysregulated function can induce adverse cardiac remodeling post-MI. Ubiquitin (UB) is a highly evolutionarily conserved small protein and is a normal constituent of plasma. Levels of UB are increased in the plasma during a variety of pathological conditions, including ischemic heart disease. Treatment of mice with UB associates with decreased inflammatory response and improved heart function following ischemia/reperfusion injury. This review summarizes the role of macrophages in the infarct healing process of the heart post-MI, and discusses the role of exogenous UB in myocardial remodeling post-MI and in the modulation of macrophage phenotype and function.

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Remote ischemic preconditioning prevents sarcolemmal-associated proteolysis by MMP-2 inhibition

Bin,

Zaobornyj,

Garces

et al. 2023

Mol Cell Biochem

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The death of myocytes occurs through different pathways, but a key point in the transition from reversible to irreversible injury is the rupture of the plasma membrane. Three major groups of structural proteins that link the extracellular and intracellular milieus and confer structural stability to the cell membrane are present in cardiac myocytes: the dystrophin-associated protein complex, the vinculinintegrin link, and the spectrin-based submembranous cytoskeleton.The objective was to determine if rIPC preserves membrane-associated cytoskeletal proteins (dystrophin and β-dystroglycan) through the inhibition of metalloproteinase type 2 (MMP-2) activity. A second objective was to describe some of the intracellular signals of the rIPC, that modify mitochondrial function and are activated during early reperfusion.Methods: Isolated rat hearts were subjected to 30 min of global ischemia and 60 min of reperfusion (I/R). rIPC was performed by 3 cycles of ischemia/reperfusion in the lower limb (rIPC). Results: As we expected, rIPC signi cantly decreased the infarct size. rIPC induced an Akt/GSK-3b phosphorylation and the inhibition of the MPTP opening, improving mitochondrial function, increasing membrane potential, ATP production and respiratory control. I/R induced ONOOproduction, which activates MMP-2. This enzyme degrades β-dystroglycan and dystrophin and collaborates to sarcolemmal disruption. Conclusion: rIPC attenuates the breakdown of β-dystroglycan and dystrophin through the inhibition of MMP-2 activity. Furthermore, rIPC activates different intracellular pathway that involves the an Akt/Gsk3b and MPTP pore with preservation of mitochondrial function.

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Post-ischemic cardioprotective potential of exogenous ubiquitin in myocardial remodeling late after ischemia/reperfusion injury

Cited by 4 publications

References 71 publications

Post-myocardial infarction fibrosis: Pathophysiology, examination, and intervention

Post-myocardial infarction fibrosis: Pathophysiology, examination, and intervention

Macrophages in the Inflammatory Phase following Myocardial Infarction: Role of Exogenous Ubiquitin

Remote ischemic preconditioning prevents sarcolemmal-associated proteolysis by MMP-2 inhibition

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