Age-Related Changes in Redox Signaling and VSMC Function

Abstract

Epidemiological studies have shown that advancing age is associated with an increased prevalence of cardiovascular disease (CVD). Vascular smooth muscle cells (VSMC) comprise the major arterial cell population, and changes in VSMC behavior, function, and redox status with age contribute to alterations in vascular remodeling and cell signaling. Over two decades of work on aged animal models provide support for age-related changes in VSMC and=or arterial tissues. Enhanced production of reactive oxygen species (ROS) and insufficient removal by scavenging systems are hallmarks of vascular aging. VSMC proliferation and migration are core processes in vascular remodeling and influenced by growth factors and signaling networks. The intrinsic link between gene regulation and aging often relates directly to transcription factors and their regulatory actions. Modulation of growth factor signaling leads to up-or downregulation of transcription factors that control expression of genes associated with VSMC proliferation, inflammation, and ROS production. Four major signaling pathways related to the transcription factors, AP-1, NF-kB, FoxO, and Nrf2, will be reviewed. Knowledge of age-related changes in signaling pathways in VSMC that lead to alterations in cell behavior and function consistent with disease progression may help in efforts to attenuate age-related CVD, such as atherosclerosis. Antioxid. Redox Signal. 12, 641-655.

Effect of morin, a flavonoid against DOCA-salt hypertensive rats: a dose dependent study

“…The animals were placed in heated chamber at an ambient temperature of (30)(31)(32)(33)(34) 曟 ) for 15 min and from each animal, [1][2][3][4][5][6][7][8][9] blood pressure values were recorded. The lowest three readings were averaged to obtain a mean blood pressure.…”

“…Hypertension is a major risk factor for cardiovascular diseases and a large body of evidence suggests oxidative stress, an increase in the production of reactive oxygen species (ROS), as a strong underlying factor in hypertension [4,5] . Excessive ROS generation has been suggested to be involved in a variety of cardiovascular diseases including hypertension, inflammation in the cardiovascular system, cardiac hypertrophy, cardiomyopathies and ischemic heart disease [6][7][8] . Various genetic and environmental factors are known to be involved in the pathogenesis of primary hypertension, among which excess sodium intake has long been regarded as the pivotal environmental factor for this disorder [9] .…”

“…Morin (3,5,7,2´,4´-pentahydroxyflavone; a light yellowish pigment) is a kind of flavonoid belonging to the group of flavonols (Figure 1), found in guava leaves [16] , onion, apple [17] Objective: To determine the protective effect of morin, a flavonoid against deoxycorticosterone acetate (DOCA)-salt induced hypertension in male Wistar rats. Methods: Hypertension was induced in uninephrectomized rats by weekly twice subcutaneous injection of DOCA (25 mg/ kg bw) and 1% NaCl in the drinking water for six consecutive weeks.…”

Role of nuclear factor (erythroid-derived 2)-like 2 in metabolic homeostasis and insulin action: A novel opportunity for diabetes treatment?

“…With the causal link of oxidative stress with insulin reJanuary 15, 2012|Volume 3|Issue 1| WJD|www.wjgnet.com 23 sistance [15,66] , it is reasonable to expect that Nrf2 activation can be the potential drug target for diabetes treatment [67][68][69][70][71] . Based on existing studies, several aspects of Nrf2 activation can benefit diabetic patients: (1) Nrf2 activation protects pancreatic β-cells from damage [65] and subsequently prevents the onset of diabetes; (2) The sensitizing action of Nrf2 on insulin may bring benefit for diabetic patients with better glucose control; (3) In addition, hyperglycemia-induced endothelial dysfunction, vascular complications and cardiomyocyte damage [72,73] may be prevented by Nrf2 activation by reducing oxidative stress [74][75][76][77] ; and (4) A protective role of the Nrf2 system in diabetic nephropathy and neuropathy is another potential function for a Nrf2 modulating drug [78][79][80][81] .…”

Inhibition of NADPH Oxidases Prevents Chronic Ethanol-Induced Bone Loss in Female Rats

“…In biological systems, ROS such as superoxide and hydrogen peroxide are ubiquitous signaling molecules, and their role in tissue physiology and pathophysiology has been extensively elucidated (Li and Fukagawa, 2010). Four members of the NADPH oxidase (Nox) enzyme family are important sources of ROS in many tissues: Nox1, Nox2, Nox3, and Nox4.…”