Vascular Aging and Stroke
Due to the gradual aging of populations, aging is a crucial topic of research and vascular aging is the research focus of the group headed by Prof. Giovanni G. Camici.
Advanced age is a major risk factor for cardiovascular diseases (CV) nevertheless its direct effects on the cardiovascular systems are not clear since it occurs in parallel to atherosclerosis and other risk factors. Animal models offer an ideal opportunity to assess the effects of aging since they do not spontaneously develop other classical cardiovascular risk factors.
Different genes such as p66Shc, JunD and Sirt1 controlling the aging process were shown to be implicated in the pathogenesis of cardiovascular disease indicating that common mechanisms may mediate both aging and cardiovascular disease. In line with this, the mammalian silent information regulator-two 1 -Sirt1- gene was shown to be implicated in aging as well as in atherosclerosis. In particular, low levels of Sirt1 have been associated with a worsened cardiovascular function in different disease conditions. In light of the above, we recently investigated the expression changes of Sirt1 gene in circulating cells (monocytes) of coronary artery disease (CAD) and acute coronary syndrome (ACS) patients (Breitenstein A et al. PLoS ONE 2013). Interestingly, we found that Sirt1 gene expression was higher in healthy subjects as compared to patients with CAD or ACS confirming previous observations that this protective gene is lost in disease conditions (Figure 1).
Similarly, we recently demonstrated that another gene -p66Shc- not only controls aging but is also involved in determining stroke size following cerebral ischemic injury as well as age-dependent dysfunction of cerebral arteries (Figure 2).
The above data underscore the tight link between aging genes, cardiovascular disease and oxidative stress indicating that a better understanding of the molecular mechanisms mediating aging may also help in the understanding of several cardiovascular diseases.
Liberale L, Bonetti NR, Puspitasari YM, Schwarz L, Akhmedov A, Montecucco F, Ruschitzka F, Beer JH, Lüscher TF, Simard J, Libby P, Camici GG Postischemic Administration of IL-1α Neutralizing Antibody Reduces Brain Damage and Neurological Deficit in Experimental Stroke. Circulation 2020 July;142:00–00. DOI: 10.1161
Liberale L, Gaul DS, Akhmedov A, Bonetti NR, Nageswaran V, Costantino S, Pahla J, Weber J, Fehr V, Vdovenko D, Semerano A, Giacalone G, Kullak-Ublick GA, Sessa M, Eriksson U, Paneni F, Ruschitzka F, Montecucco F, Beer JH, Lüscher TF, Matter CM, Camici GG Endothelial SIRT6 blunts stroke size and neurological deficit by preserving blood-brain barrier integrity: a translational study. Eur Heart J. 2020 Apr 21;41(16):1575-1587.
Liberale L, Montecucco F, Tardif JC, Libby P, Camici GG. Inflamm-ageing: the role of inflammation in age-dependent cardiovascular disease. Eur Heart J. 2020 Feb 1. pii: ehz961.
Diaz-Cañestro C, Reiner MF, Bonetti NR, Liberale L, Merlini M, Wüst P, Amstalden H, Briand-Schumacher S, Semerano A, Giacalone G, Sessa M, Beer JH, Akhmedov A, Lüscher TF, Camici GG. AP-1 (Activated Protein-1) Transcription Factor JunD Regulates Ischemia/Reperfusion Brain Damage via IL (Interleukin)-1β. Stroke. 2019 Feb;50(2):469-477
Paneni F, Diaz Cañestro C, Libby P, Lüscher TF, Camici GG The Aging Cardiovascular System: Understanding It at the Cellular and Clinical Levels
J Am Coll Cardiol. 2017 Apr 18;69(15):1952-1967
Shi Y, Savarese G, Perrone-Filardi P, Lüscher TF, Camici GG Enhanced age-dependent cerebrovascular dysfunction is mediated by adaptor protein p66Shc. Int J Cardiol. 2014 Jun 27
Spescha RD, Glanzmann M, Simic B, Witassek F, Keller S, Akhmedov A, Tanner FC, Lüscher TF, Camici GG Adaptor Protein p66Shc Mediates Hypertension-Associated, Cyclic Stretch-Dependent, Endothelial Damage. Hypertension. 2014 May 19
Spescha RD, Shi Y, Wegener S, Keller S, Weber B, Wyss MM, Lauinger N, Tabatabai G, Paneni F, Cosentino F, Hock C, Weller M, Nitsch RM, Lüscher TF and Camici GG Deletion of the ageing gene p66Shc reduces early stroke size following ischaemia/reperfusion brain injury. Eur Heart J. 2013 Jan;34(2):96-103
- Breitenstein A, Wyss CA, Spescha RD, Franzeck FC, Hof D, Riwanto M, Hasun M, Akhmedov A, von Eckardstein A, Maier W, Landmesser U, Lüscher TF, Camici GG Peripheral blood monocyte sirt1 expression is reduced in patients with coronary artery disease. PLoS One. 2013;8(1):e53106