Milk Fat Globule Epidermal Growth Factor VIII Fragment Medin in Age-Associated Arterial Adverse Remodeling and Arterial Disease.

Medin, a small 50-amino acid peptide, is an internal cleaved product from the second discoidin domain of milk fat globule epidermal growth factor VIII (MFG-E8) protein. Medin has been reported as the most common amylogenic protein in the upper part of the arterial system, including aortic, temporal, and cerebral arterial walls in the elderly. Medin has a high affinity to elastic fibers and is closely associated with arterial degenerative inflammation, elastic fiber fragmentation, calcification, and amyloidosis.

Inflammatory Role of Milk Fat Globule-Epidermal Growth Factor VIII in Age-Associated Arterial Remodeling.

Background Age-associated aortic remodeling includes a marked increase in intimal medial thickness (IMT), associated with signs of inflammation. Although aortic wall milk fat globule-epidermal growth factor VIII (MFG-E8) increases with age, and is associated with aortic inflammation, it is not known whether MFG-E8 is for the age-associated increase in aortic IMT. Here, we tested whether MFG-E8 is for the age-associated increase in aortic IMT.

Age-associated proinflammatory elastic fiber remodeling in large arteries.

Elastic fibers are the main components of the extracellular matrix of the large arterial wall. Elastic fiber remodeling is an intricate process of synthesis and degradation of the core elastin protein and microfibrils accompanied by the assembly and disassembly of accessory proteins. Age-related morphological, structural, and functional proinflammatory remodeling within the elastic fiber has a profound effect upon the integrity, elasticity, calcification, amyloidosis, and stiffness of the large arterial wall.

Proinflammation, profibrosis, and arterial aging.

Aging is a major risk factor for quintessential cardiovascular diseases, which are closely related to arterial proinflammation. The age-related alterations of the amount, distribution, and properties of the collagen fibers, such as cross-links and degradation in the arterial wall, are the major sequelae of proinflammation. In the aging arterial wall, collagen types I, II, and III are predominant,  and are mainly produced by stiffened vascular smooth muscle cells (VSMCs) governed by proinflammatory signaling, leading to profibrosis.

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

Background Aging exponentially increases the incidence of morbidity and mortality of quintessential cardiovascular disease mainly due to arterial proinflammatory shifts at the molecular, cellular, and tissue levels within the arterial wall. Calorie restriction ( CR ) in rats improves arterial function and extends both health span and life span. How CR affects the proinflammatory landscape of molecular, cellular, and tissue phenotypic shifts within the arterial wall in rats, however, remains to be elucidated.

Proinflammatory Arterial Stiffness Syndrome: A Signature of Large Arterial Aging.

Age-associated structural and functional remodeling of the arterial wall produces a productive environment for the initiation and progression of hypertension and atherosclerosis. Chronic aging stress induces low-grade proinflammatory signaling and causes cellular proinflammation in arterial walls, which triggers the structural phenotypic shifts characterized by endothelial dysfunction, diffuse intimal-medial thickening, and arterial stiffening. Microscopically, aged arteries exhibit an increase in arterial cell senescence, proliferation, invasion, matrix deposition, elastin fragmentation, calcification, and amyloidosis.

Reduced vasorin enhances angiotensin II signaling within the aging arterial wall.

The glycosylated protein vasorin physically interacts with the transforming growth factor-beta1 (TGF-β1) and functionally attenuates its fibrogenic signaling in the vascular smooth muscle cells (VSMCs) of the arterial wall. Angiotensin II (Ang II) amplifies TGF-β1 activation in the VSMCs of the arterial wall with aging. In this study, we hypothesized that a reduced expression of the protein vasorin plays a contributory role in magnifying Ang II-associated fibrogenic signaling in the VSMCs of the arterial wall with aging.