Age- and sex-dependent alteration of functions and epigenetic modifications of vessel and endothelium related biomarkers

Abstract

Introduction Aging is a natural process for every living organism. The trouble here is increased health problems as a result of aging. Aging is a dominant risk factor for cardiovascular diseases and is associated with progressive vascular dysfunction (Herrera et al., 2010; Laurent, 2012). Many studies reported a sex difference in age-associated vascular changes (Sarabi et al., 1999; Sader and Celermajer, 2002; Okumura et al., 2011). Celermajer et al. (1994) showed that age-related impairment in endothelial function appeared to occur earlier in males than in females. Different regulation of endothelial function is one of the main mechanisms underlying the variation in age-associated vascular changes in females and males (Sarabi et al., 1999). However, the underlying mechanisms of sex-dependent alterations in endothelial function remain to be investigated. Endothelium-derived NO plays a key role in the regulation of vascular homeostasis (Moncada et al., 1991). The capacity of NO release is considered to be a major indicator of endothelial function. Vascular aging characterized by endothelial dysfunction is associated with reduced NO bioavailability and increased generation of reactive oxygen species (ROS). ROS combine with NO and produce deleterious free radicals, leading to endothelial dysfunction (Heitzer et al., 2001; Tsimakis, 2006; El Assar et al., 2013; Rochette et al., 2013). ADMA is an endogenous competitive inhibitor of NO synthase and an increase in ADMA is associated with impairment of NO synthesis (Bouras et al., 2013; Sverdlov et al., 2014). It has been reported that plasma concentrations of ADMA increase in elderly people and in postmenopausal women (Schulze et al., 2005). H 2 S is acknowledged as an important gaseous signaling molecule (Kolluru et al., 2013). It has been revealed that H 2 S is an endogenous regulator of oxidative damage and aging in C. elegans (Qabazard et al., 2014). However, the relationship between these molecules and endothelial function in the aging process is still largely unknown. Recent studies have focused on epigenetic changes that occur as a hallmark of aging (Brunet and Berger, 2014).

Sexo e idade e sua influência sobre a anatomia da aorta abdominal e seus ramos

“…[17][18][19][20][21][22] The SMA also exhibited greater changes in angle and diameter in men. The lesser predisposition towards changes in arterial anatomy among women may be related to the role played by estrogen, 6,9,22 which increases the bioavailability of nitric oxide (NO) without increasing expression and/or activity of endothelial nitric oxide-synthase (eNOS), which has antioxidant properties that may induce or accelerate vascular aging. 6,8,9 Nitric oxide bioavailability is essential for normal endothelial function and it is known that advanced age leads to compromised endothelial NO production and increased NO inactivation by superoxide, contributing to age-related endothelial dysfunction.…”

“…The lesser predisposition towards changes in arterial anatomy among women may be related to the role played by estrogen, 6,9,22 which increases the bioavailability of nitric oxide (NO) without increasing expression and/or activity of endothelial nitric oxide-synthase (eNOS), which has antioxidant properties that may induce or accelerate vascular aging. 6,8,9 Nitric oxide bioavailability is essential for normal endothelial function and it is known that advanced age leads to compromised endothelial NO production and increased NO inactivation by superoxide, contributing to age-related endothelial dysfunction. 6,10,16,23,24 The most notable characteristics of vascular aging described in the literature are the mechanical and structural changes to vessel walls, including arterial dilation and thickening, primarily seen in the abdominal aorta and highlighted in many publications.…”

“…6,8,9 Nitric oxide bioavailability is essential for normal endothelial function and it is known that advanced age leads to compromised endothelial NO production and increased NO inactivation by superoxide, contributing to age-related endothelial dysfunction. 6,10,16,23,24 The most notable characteristics of vascular aging described in the literature are the mechanical and structural changes to vessel walls, including arterial dilation and thickening, primarily seen in the abdominal aorta and highlighted in many publications. 5,12,15,22,25 Arterial changes over the course of life are also influenced by modifiable cardiovascular risk factors, such as hypertension, obesity, smoking, and lifestyle, and also by unmodifiable factors, such as genetics, age, and family history.…”

“…Aging causes structural and functional changes, particularly in the major arteries. [5][6][7][8][9][10][11] These changes result in increased vascular rigidity due to increased production and deposition of collagen and loss of elastin fibers, primarily in the tunica media of large and medium arteries. 5,9,10,[12][13][14] Vascular rigidity has been known as a risk factor for cardiovascular diseases since the nineteenth century.…”

“…9,14 However, noninvasive methods that enable the anatomy and physiology of the circulatory system to be studied (blood flow, diameter, angles, and other details), relating them to their clinical repercussions and utilities, have only recently become available. 13,14 Studies have already proven that aging affects vascular changes differently in men and women and while there is already evidence of biochemical and functional differences, 6 much still remains to be investigated in relation to the changes to the arterial anatomy that occur as aging advances and in relation to how patient sex influences these changes.…”