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Spermine and spermidine reversed age-related cardiac deterioration in rats
Hao Zhang1, Junying Wang1, Lingxu Li1
1Department of Pathophysiology, The Key Laboratory of Cardiovascular Pathophysiology, Harbin Medical University, Harbin, China.
Insights
Polyamines like spermine (SP) and spermidine (SPD) can reverse age-related heart changes. These compounds show potential as clinical therapies for cardiovascular disease in aging hearts.
Area of Science:
- Cardiovascular Science
- Aging Research
- Molecular Biology
Background:
- Aging is a primary risk factor for cardiovascular disease (CVD).
- Polyamines, spermine (SP) and spermidine (SPD), are vital for cellular functions and decline with age.
- Understanding polyamine effects on the aging heart is crucial for developing interventions.
Purpose of the Study:
- To investigate the impact of exogenous spermine (SP) and spermidine (SPD) on age-related changes in the aging rat heart.
- To identify molecular pathways affected by SP and SPD in the aging myocardium.
Main Methods:
- Administration of SP or SPD to aged rats (22-24 months old) for 6 weeks.
- Assessment of myocardial morphology, fibrosis, and apoptosis.
- Combined proteomics and metabolomics analyses to identify differentially expressed proteins and metabolites.
Main Results:
- SP and SPD treatments reversed age-related myocardial alterations, fibrosis, and apoptosis.
- SP and SPD modulated specific proteins and metabolites involved in immune response, blood coagulation, lipid, and glutathione metabolism.
- Proteomic and metabolomic analyses revealed distinct molecular changes induced by SP and SPD.
Conclusions:
- Polyamines (SP and SPD) exert significant cardioprotective effects in the aging heart.
- These polyamines reverse detrimental age-related cardiac changes at a molecular level.
- SP and SPD represent promising therapeutic candidates for age-related cardiovascular diseases.
Abstract:
Aging is the most important risk factor for cardiovascular disease (CVD). Slowing or reversing the physiological impact of heart aging may reduce morbidity and mortality associated with age-related CVD. The polyamines, spermine (SP) and spermidine (SPD) are essential for cell growth, differentiation and apoptosis, and levels of both decline with age. To explore the effects of these polyamines on heart aging, we administered SP or SPD intraperitoneally to 22- to 24-month-old rats for 6 weeks. Both treatments reversed and inhibited age-related myocardial morphology alterations, myocardial fibrosis, and cell apoptosis. Using combined proteomics and metabolomics analyses, we identified proteins and metabolites up- or downregulated by SP and SPD in aging rat hearts. SP upregulated 51 proteins and 28 metabolites while downregulating 80 proteins and 29 metabolites. SPD upregulated 44 proteins and 24 metabolites and downregulated 84 proteins and 176 metabolites. These molecules were mainly associated with immune responses, blood coagulation, lipid metabolism, and glutathione metabolism pathways. Our study provides novel molecular information on the cardioprotective effects of polyamines in the aging heart, and supports the notion that SP and SPD are potential clinical therapeutics targeting heart disease.