Atherosclerosis and Cardiovascular Diseases in Progeroid Syndromes

Abstract

Hutchinson-Gilford progeria syndrome (HGPS) and Werner syndrome (WS) are two of the representative genetic progeroid syndromes and have been widely studied in the field of aging research. HGPS is a pediatric disease in which premature aging symptoms appear in early childhood, and death occurs at an average age of 14.5 years, mainly due to cardiovascular disease (CVD). Conversely, WS patients exhibit accelerated aging phenotypes after puberty and die in their 50s due to CVD and malignant tumors. Both diseases are models of human aging, leading to a better understanding of the aging-associated development of CVD. In this review, we discuss the pathogenesis and treatment of atherosclerotic diseases presented by both progeroid syndromes with the latest findings. Hutchinson-Gilford Progeria SyndromeHGPS is an ultra-rare autosomal dominant genetic premature aging syndrome that occurs in one in four to eight million births and causes death at an average age of 14.5 years due to myocardial infarction or stroke 4, 5) (Table 1). Because of the abnormal splicing of the LMNA gene on chromosome 1, the lamin A protein encoded by this gene cannot be normally produced, and an abnormal protein called progerin accumulates in the nucleus. The main symptoms are scleroderma-like skin, joint contractures, bone abnormalities, hair loss, growth retardation, and atherosclerotic diseases, such as myocardial infarction and stroke. Clinical Characteristics of HGPSInfants with HGPS are normal at birth, but the mean weight is slightly small for gestational age 4) . The first pathognomonic signs are prominent veins on the nose bridge, followed by growth retardation, hair loss, and reduced subcutaneous fat around 6 to 12 months, and the diagnosis is often made between 2 and 3 years Copyright©2021 Japan Atherosclerosis Society This article is distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License.

Lifetime extension and the recent cause of death in Werner syndrome: a retrospective study from 2011 to 2020

“…In addition, in a recent autopsy of a patient with WS who died at age 76, there were almost no atherosclerotic changes in the cerebral vessels and no stenosis in the coronary arteries [ 7 , 12 ]. A number of other recent case reports have also shown that atherosclerotic changes were absent or slightly present [ 13 , 14 ]. These findings suggest that atherosclerotic diseases are being controlled in WS.…”

Renal dysfunction, malignant neoplasms, atherosclerotic cardiovascular diseases, and sarcopenia as key outcomes observed in a three-year follow-up study using the Werner Syndrome Registry

“…A clinical trial with nicotinamide riboside, a precursor of NAD, which may be effective for intractable ulcers, sarcopenia, and ASCVD, is investigating the safety and efficacy in patients with Werner syndrome [ 66 ]. Using state-of-the-art technologies, such as genome, transcriptome, and epigenome analyses [ 67 ], study of the generation of iPS cells from patients with Werner syndrome and the correction of the WRN gene by the CRISPR/Cas9-mediated methods [ 68 ] will create new treatments for patients with Werner syndrome.…”

Premature aging in genetic diseases: what conclusions can be drawn for physiological aging

“…These may implicate common vascular changes in affected brain regions in CS and elderly. Atherosclerosis appears to be an atypical feature in CS patients ( Hayashi et al, 2012 ) in contrast to HGPS and WS ( Kato and Maezawa, 2022 ). Recent studies in CS mouse model, Csa−/−Xpa−/− , found no changes in isolated endothelial cells or aorta ( Kajitani et al, 2021 ) suggesting rather non-cell autonomous effects ( Table 1 ) as an underlying cause for brain vascular defects thereby favoring the hypothesis of neural-centric view of aging in CS ( Figure 3 ).…”