Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Abdellatif, M.
Cardioprotective mechanisms of spermidine in aging and related cardiovascular disease
PhD-Studium (Doctor of Philosophy); Humanmedizin; [ Dissertation ] Graz Medical University; 2019. pp. 141
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Marsche Gunther
- Rainer Peter
- Sedej Simon
- Altmetrics:
- Abstract:
- Due to an ever-increasing population aging worldwide, the prevalence of cardiovascular diseases is progressively growing and, thus, imposing a massive medical and economic burden on society. In this regard, caloric restriction has shown promising cardiovascular and health-promoting effects. However, caloric restriction cannot be broadly implemented as it does not appeal the majority of people, not to mention its uncertain safety profile in the elderly. Therefore, more feasible alternatives, especially pharmaceutical or natural dietary compounds that mimic caloric restriction, are currently needed. To this end, we found that supplementing the natural polyamine and caloric restriction mimetic spermidine induces a myriad of cardiovascular health-promoting effects. Specifically, aged mice treated later in their life with 3 mM spermidine showed improvements in most aspects of age-related cardiac decline, including hypertrophy, diastolic function, and ventricular-vascular coupling. Consistently, spermidine feeding to an animal model of hypertension and related cardiomyopathy revealed similar cardioprotective, in addition to, anti-hypertensive effects. Mechanistically, spermidine seemed to act via two, not necessarily exclusive, routes; Firstly, spermidine boosted autophagy and mitophagy in the heart and kidneys, which improved cardiomyocyte structure and function and possibly also contributed to better blood pressure control. Secondly, exogenous spermidine administration spared its precursor arginine from being utilized for polyamines biosynthesis and, instead, might have redirected arginine metabolism towards replenishing the nitric oxide (NO) bioavailability, which is indispensable for cardiovascular health. Spermidine also had an anti-inflammatory effect, which might limit NO breakdown and, thus, further improve NO bioavailability. In humans, we found spermidine concentrations in the heart to constantly decline with age. More importantly, we detected a compensatory increase in cardiac spermidine levels in heart failure patients, whereas individuals reporting higher dietary intake of spermidine had reduced blood pressure and lower incidence of cardiovascular disease, and related mortality. Taken together, the results presented in this thesis provide sufficient evidence for clinical testing of spermidine in humans to delay cardiac aging and, possibly, related late-life disorders.