P6495Role of vascular smooth muscles cells in naked mole rats during ageing (Heterocephalus glaber)

Abstract

Abstract Vascular stiffening and a prothrombotic state consistently increase with age. We have shown previously that Vascular Smooth Muscle Cells (VSMCs) have a major role in both vascular stiffening and thrombin generation in the vascular wall in a context of hypertension (Arterioscler Thromb Vasc Biol 2015). Naked mole rats (NMRs) are the longest-lived rodent species, have a maximum lifespan exceeding 30 years, living approximately ten times longer than a similarly sized mouse, and do not develop arterial stiffening with age (AJP, 2014). The objective was to analyze arterial composition as well as phenotypic VSMC changes from primary cultures in NMRs at 2- and 10-year old. We used Thoracic aortas of young (2-year-old) and adult (10-year-old) NMRs for the study of arterial wall as well as for the preparation of VSMCs' primary cultures. Our results showed no difference in elastin/collagen ratio and no intimal thickening in NMRs at 10-years-old compared to 2-years-old (n=4 in each group). Primary cultures showed positive alpha-actin staining without VSMC morphological changes up to 6 passages using standard conditions (20% fetal bovine serum). Smoothelin and myosin-heavy chain are similar at both ages. VSMCs density was identical in 2- and 10-years-old NMRs, whereas cell hypertrophy was observed in older animals. Focal adhesions assessed by vinculin staining were unchanged between the two groups. There was no increase in plasma thrombin generation and at the surface of VSMCs up to 10 years of age associated with no increase in fibrinogen and factor VIII, both known to increase normally with age in humans. Our findings showed an absence of canonical signs of normal vascular ageing in NMRs that are normally present in rodent and humans. The retaining of a VSMC phenotype and focal adhesion distribution support previous data observed in ageing. These results reinforce the current concept of VSMCs as emergent cells in the process of ageing.