Chronic Coronary Artery Disease: Wall Disease vs. Lumenopathy

Abstract

Acute and chronic coronary artery disease (CAD) are interconnected, representing two facets of the same condition. Chronic CAD exhibits a dynamic nature, manifesting as stable or acute ischemia, or both. Myocardial ischemia can be transient and reversible. The genesis of CAD involves diverse anatomical and functional mechanisms, including endothelial dysfunction, arteriolar remodeling, capillary rarefaction, and perivascular fibrosis, though no single factor explains its heterogeneity. Chronic CAD is often stable but may present as symptomatic or asymptomatic (e.g., in diabetes) and affect various coronary compartments (epicardial or microcirculation). This complexity necessitates a reappraisal of our approach, as pathophysiological mechanisms vary and often overlap. A comprehensive exploration of these mechanisms using advanced diagnostic techniques can aid in identifying the dynamic processes underlying CAD. The disease may present as obstructive or non-obstructive, stable or unstable, underscoring its diversity. The primary source of CAD lies in the arterial wall, emphasizing the need for research on its components, such as the endothelium and vascular smooth muscle cells, and factors disrupting arterial homeostasis. Shifting focus from arterial luminal status to the arterial wall can provide insights into the genesis of atheromatous plaques, enabling earlier interventions to prevent their development and progression.

Keywords: chronic coronary artery disease; lumenopathy; myocardial ischemia; wall disease.

Figure 1

Coronary artery wall disease categorization. Stable and unstable stages can be presented in an interplay fashion.

Figure 2

Endothelial homeostatic dysfunction (in yellow) due to multiple risk factors (in blue) leads to the disequilibrium of several endothelial properties (in orange) that, in turn, promote the beginning and progression of coronary artery wall disease. VSMC: vascular smooth muscle cell.

Figure 3

Sequence of progression when endothelial affection occurs. It begins as a wall disease whereas luminal disease represents the epiphenomenon of the wall disease. VSMC: vascular smooth muscle cell.

Figure 4

Proposed therapeutic targets at the early stage of atherosclerosis, at the very beginning of endothelial homeostatic dysfunction. The vascular tone, the proliferation/migration of VSMC cells, and the immune adhesion cell activation might be regulated. VSMC: vascular smooth muscle cells; Nur77: nuclear receptor subfamily 4 group A member 1; Tetrahydrobipterin (BH4): enzymatic cofactor; Treg: T immune regulator cells. See text for more details; IL10: interleukin 10; LDL: low-density lipoprotein.