• 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2020-03
  • 2020-07
  • 2020-08
  • 2021-03
  • br Clinical aspects of EC senescence


    Clinical aspects of EC senescence in aging-related arterial stiffness and systolic hypertension Cellular senescence is a physiological or pathological processes throughout life [7]. In physiological condition, cell senescent is involved in Omadacycline ic50 tissue development, tissue repair, as well as tumor suppression responses [7]. However, the accumulation of cell senescent can lead to loss of replicative capacity, cell apoptosis, and adverse structural changes, and associated CVD [7]. Cellular senescence is usually linked with aging and age-related disorders. In human coronary arteries, ECs with increased β-galactosidase activity associated with enhanced senescence are observed during aging, suggesting that aging is also associated with reduced EC regenerative and EC senescence that is associated with a reduction of EC dependent arterial relaxation [8]. To this point, a reduction of EPC is associated with the development of arterial stiffness in patients with psoriasis [9]. Studies have found that NO donors reduce arterial stiffness in healthy subjects and patients with hypertension and hypercholesterolemia [10]. These data support a role of EC senescence in the pathogenesis of CVD. However, while few clinical studies have explored the relationship between EC senescence, arterial stiffness and hypertension those done have shown that aging is closely associated with arterial stiffness and CVD. For instance, data from the Framingham study found that advancing age was significantly associated with a higher carotid-femoral pulse wave velocity and mean arterial pressure [11]. Meanwhile, arterial stiffness has been regarded as an independent predictor of CVD morbidity and mortality in the general population, aging, hypertensive patients, as well as patients with end-stage renal disease [12]. With aging and associated arterial stiffness, systolic pressure tends to increase whereas diastolic pressure tends to decline and this pathophysiological change elevates pulse pressure and aortic pulse wave velocity. Indeed, the prevalence of hypertension, particularly isolated systolic hypertension in aging population is increased [13]. Increased systolic pressure increases left ventricular afterload with associated increases in myocardial oxygen requirements. The falling diastolic pressure decreases the perfusion of coronary circulation during diastole. These consequences of arterial stiffness, the increased systolic pressure and decreased diastolic pressure further induce left ventricular hypertrophy, myocardial ischemia, remodeling and other cardiovascular complications in aging individuals [1]. Invasive methods including the quantitative angiography and intracoronary Doppler and non-invasive methods including venous occlusion plethysmography, flow-mediated dilatation in brachial artery, and peripheral arterial tonometry have been applied to investigate endothelial and vascular function [1].
    Mechanisms of aging-related EC senescence Factors including cell cycle dysregulation, oxidative stress, calcium (Ca2+) signaling, inflammation, activated renin angiotensin-aldosterone system (RAAS), and hyperuricemia in aging induce EC senescence. However, accumulated EC senescence also aggravates aging-related inflammation, oxidative, and vascular dysfunction with a feedback manner (Fig. 1).
    Pathophysiological changes in aging-related EC senescence
    Molecular signaling related EC senescence
    Genetic and epigenetic regulation in EC senescence
    Conclusions EC senescence is an important contributor in aging-induced vascular dysfunction. Cardinal features of vascular aging include increases in arterial stiffness, and systolic pressure. Abnormal expression and activation of NO, EDHF, Ca2+ signaling, increased endothelium permeability, impairment of angiogenesis and vascular repair, and reduction of EC mitochondrial biogenesis contribute to the pathophysiological changes in EC senescence and aging associated vascular dysfunction. Cell cycle regulation, oxidative stress, increased ROS, altered Ca2+ signaling, hyperuricemia, and vascular inflammation are involved in the pathophysiological process. Molecular proteins and signaling pathways including Sirt1, Klotho, FGF21, activation of RAAS contribute to these pathophysiological changes. Further, accumulation of genetic damage and epigenetic alterations change the normal gene expression and activity, resulting in cellular senescence and vascular dysfunction. While cellular senescence impacts vascular function and induce CVD, cellular senescence also plays a beneficial role in prevention of human disease including cancer. Indeed, cellular senescence is a physiological event in repair of adult tissues. Therefore, further studies of EC senescence are necessary in order to better understand the precise mechanisms and to develop potential strategies in prevention of age-related CVD.