Emerging Molecular Determinants and Protective Strategies in Heart Disease: What’s New in the Journal of Clinical Medicine? Outlook to the Future

Rocca, Carmine; Angelone, Tommaso

doi:10.3390/jcm12144564

Cited by 1 publication

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“…Despite the progress of pharmacological and nonpharmacological therapy in limiting and/or reversing the signs and symptoms of HF, mortality and morbidity related to this multifactorial syndrome remain elevated. Thus, identifying additional strategies to support earlier detection and treatment and deciphering key pathophysiological pathways to be targeted for achieving maximal clinical benefit in patients with HF still represents a critical medical issue [ 11 , 46 ]. The key role of the oxidoreductase SELENOT in cardiomyocyte differentiation and acute cardioprotection [ 19 , 21 , 22 ] pointed out this selenoprotein as an emerging regulator of cardiac development and function while raising an important unaddressed point concerning the beneficial action of this protein in chronic settings of cardiac dysfunction.…”

Section: Discussionmentioning

confidence: 99%

The redox-active defensive Selenoprotein T as a novel stress sensor protein playing a key role in the pathophysiology of heart failure

De Bartolo,

Pasqua,

Romeo

et al. 2024

J Transl Med

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Maladaptive cardiac hypertrophy contributes to the development of heart failure (HF). The oxidoreductase Selenoprotein T (SELENOT) emerged as a key regulator during rat cardiogenesis and acute cardiac protection. However, its action in chronic settings of cardiac dysfunction is not understood. Here, we investigated the role of SELENOT in the pathophysiology of HF: (i) by designing a small peptide (PSELT), recapitulating SELENOT activity via the redox site, and assessed its beneficial action in a preclinical model of HF [aged spontaneously hypertensive heart failure (SHHF) rats] and against isoproterenol (ISO)-induced hypertrophy in rat ventricular H9c2 and adult human AC16 cardiomyocytes; (ii) by evaluating the SELENOT intra-cardiomyocyte production and secretion under hypertrophied stimulation. Results showed that PSELT attenuated systemic inflammation, lipopolysaccharide (LPS)-induced macrophage M1 polarization, myocardial injury, and the severe ultrastructural alterations, while counteracting key mediators of cardiac fibrosis, aging, and DNA damage and restoring desmin downregulation and SELENOT upregulation in the failing hearts. In the hemodynamic assessment, PSELT improved the contractile impairment at baseline and following ischemia/reperfusion injury, and reduced infarct size in normal and failing hearts. At cellular level, PSELT counteracted ISO-mediated hypertrophy and ultrastructural alterations through its redox motif, while mitigating ISO-triggered SELENOT intracellular production and secretion, a phenomenon that presumably reflects the extent of cell damage. Altogether, these results indicate that SELENOT could represent a novel sensor of hypertrophied cardiomyocytes and a potential PSELT-based new therapeutic approach in myocardial hypertrophy and HF. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

The redox-active defensive Selenoprotein T as a novel stress sensor protein playing a key role in the pathophysiology of heart failure

De Bartolo,

Pasqua,

Romeo

et al. 2024

J Transl Med

Self Cite

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Emerging Molecular Determinants and Protective Strategies in Heart Disease: What’s New in the Journal of Clinical Medicine? Outlook to the Future

Abstract: Cardiovascular diseases (CVD), including coronary heart disease (CHD), heart attacks, stroke, heart failure (HF), and peripheral artery disease, still represent the leading cause of death globally, taking an estimated 17 [...]

Cited by 1 publication

References 12 publications

The redox-active defensive Selenoprotein T as a novel stress sensor protein playing a key role in the pathophysiology of heart failure

The redox-active defensive Selenoprotein T as a novel stress sensor protein playing a key role in the pathophysiology of heart failure

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