Mechanisms of arterial remodeling: lessons from genetic diseases - PubMed (original) (raw)

Mechanisms of arterial remodeling: lessons from genetic diseases

Bernard J van Varik et al. Front Genet. 2012.

Abstract

Vascular disease is still the leading cause of morbidity and mortality in the Western world, and the primary cause of myocardial infarction, stroke, and ischemia. The biology of vascular disease is complex and still poorly understood in terms of causes and consequences. Vascular function is determined by structural and functional properties of the arterial vascular wall. Arterial stiffness, that is a pathological alteration of the vascular wall, ultimately results in target-organ damage and increased mortality. Arterial remodeling is accelerated under conditions that adversely affect the balance between arterial function and structure such as hypertension, atherosclerosis, diabetes mellitus, chronic kidney disease, inflammatory disease, lifestyle aspects (smoking), drugs (vitamin K antagonists), and genetic abnormalities [e.g., pseudoxanthoma elasticum (PXE), Marfan's disease]. The aim of this review is to provide an overview of the complex mechanisms and different factors that underlie arterial remodeling, learning from single gene defect diseases like PXE, and PXE-like, Marfan's disease and Keutel syndrome in vascular remodeling.

Keywords: arterial remodeling; calcification; genetic disease; vitamin K; vitamin K-antagonists.

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Figures

Figure 1

Figure 1

Types of vascular remodeling. Adapted from Mulvany et al. (1996). Different types of arterial remodeling can be distinguished: hypotrophic (left column), eutrophic (center column) and hypertrophic (right column). In addition remodeling can be either inward or outward. Hypotrophic remodeling results in a relative thinner wall and a lower wall-to-lumen ratio. Conversely hypertrophic remodeling is characterized by thickening of the vascular wall due to cellular hyperplasia and/or hypertrophy or deposition of extracellular matrix material and results in increased wall-to-lumen ratio. When the diameter of the vessel changes but the wall-to-lumen ratio remains the same it is called eutrophic remodeling. All types of arterial remodeling can occur in cardiovascular disease, depending on the underlying pathophysiology (e.g., aneurysm or hypertensive arterial stiffening) and arterial site (e.g., central elastic arteries vs. peripheral resistance arteries).

Figure 2

Figure 2

Pathophysiological mechanisms of arterial remodeling. Cross sectional schematic view of the arterial wall. (A) Normal situation. (B) Arterial remodeling. Arterial remodeling is characterized by thickening of the wall. Elastic fiber degradation, extracellular matrix calcification and collagen deposition lead to adaptation of the vascular wall. Abbreviations: TGF-β, transforming growth factor-beta; IL-1, interleukin 1; MMP, matrix metalloproteinases; VSMC, vascular smooth muscle cell.

Figure 3

Figure 3

Pathophysiological pathways leading to arterial remodeling in genetic and cardiovascular disease. Abbreviations: PXE, pseudoxanthoma elasticum; MMP, matrix metalloproteinases; VSMC, vascular smooth muscle cell; GGCX, gamma glutamyl transferase.

Figure 4

Figure 4

Hemodynamic changes in arterial stiffening. (A) Aortic blood pressure waveform of a healthy, normotensive person. The forwards traveling wave precedes the (backwards traveling) reflected wave. (B) Aortic pressure waveform of a person with arterial stiffness. Due to increased pulse wave velocity, the forward traveling wave and reflected wave are summated leading to augmented pulse pressure.

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