Age-associated pro-inflammatory remodeling and functional phenotype in the heart and large arteries

Abstract

The aging population is increasing dramatically. Aging–associated stress simultaneously drives proinflammatory remodeling, involving angiotensin II and other factors, in both the heart and large arteries. The structural remodeling and functional changes that occur with aging include cardiac and vascular wall stiffening, systolic hypertension and suboptimal ventricular-arterial coupling, features that are often clinically silent and thus termed a silent syndrome. These age-related effects are the result of responses initiated by cardiovascular proinflammatory cells. Local proinflammatory signals are coupled between the heart and arteries due to common mechanical and humoral messengers within a closed circulating system. Thus, targeting proinflammatory signaling molecules would be a promising approach to improve age-associated suboptimal ventricular-arterial coupling, a major predisposing factor for the pathogenesis of clinical cardiovascular events such as heart failure.

Calorie Restriction Curbs Proinflammation That Accompanies Arterial Aging, Preserving a Youthful Phenotype

“…PDGF‐BB is not only a potent mitogen, but also a strong chemoattractant of VSMCs, creating a permissive tissue microenvironment for VSMC migration and invasion, promoting formation of a thickened intima in vivo 1, 2, 3, 8, 41, 42. Prior findings indicate that PDGF‐BB treatment induces invasion and migration of old VSMCs in vitro 8, 9.…”

“…Intimal thickening, collagen deposition, and elastin fragmentation are reliable indications of adverse arterial remodeling, which are closely associated with an increase in the prevalence and severity of age‐associated quintessential cardiovascular disease such as atherosclerosis due to either a reduction of threshold or an enhancement of susceptibility to hostile stimuli, for example, hyperlipidemia 1, 3, 31. Findings from both experimental animal models and human studies indicate that CR has numerous beneficial effects on arterial structural and functional remodeling and eventually decelerates biological aging 14, 15, 16, 32, 33, 34, 35, 36, 37, 38, 39.…”

“…Aging exponentially increases the incidence of morbidity and mortality of quintessential cardiovascular disease mainly due to arterial wall proinflammatory phenotypic shifts at the molecular, cellular, and tissue levels 1, 2, 3. Increases in the local arterial wall proinflammatory molecules, platelet‐derived growth factor (PDGF), matrix metalloproteinase type II (MMP2) and transforming growth factor beta 1 (TGF‐β1), promote cellular and matrix phenotypic shifts that contribute to aortic wall thickening and stiffening that accompany advancing age in mammals, a prominent arterial phenotype of biological aging 4, 5, 6, 7, 8, 9.…”

Macromolecular Degradation Systems and Cardiovascular Aging

“…Despite this limitation, multiple experimental models, including aging, Ang II stimulation, and pressure overload are thought to be useful in investigating the mechanism and implication in cardiac senescence. 2,3 Although the chronic stimulation of Ang II in mice is a well-known model of cardiac hypertrophy, recent evidence suggests that Ang II is a strong inducer of cellular senescence in several cell types other than cardiomyocytes. Moreover, it can also mediate the proinflammatory profile observed in an aged heart.…”

“…Herein, we define aging and senescence as a decline in normal physiological functioning, including the robustness and flexibility observed in mature organisms over time. In general, it is thought that proinflammatory cytokines and neurohumoral factors, such as angiotensin II (Ang II), are involved in senescence progression, ie, a decline in physiological functioning caused by aging, 3,4 and multiple signaling pathways play dominant roles in the aging process. At the cellular level, aging and senescence represent the declining cellular capacity for proliferation or regeneration.…”