Comparative characteristics of in vitro models for studying angiogenesis in cardiovascular disease

Abstract

Angiogenesis is a central mechanism in the development and progression of cardiovascular diseases. Experimental approaches for studying angiogenesis vary widely, and their translational value depends strongly on model characteristics. We aimed to provide a comparative analysis of contemporary in vitro models used to study angiogenesis and to assess their potential applicability in cardiovascular medicine. Fifty-four publications by domestic and international authors were analyzed. 2D models remain accessible tools for investigating endothelial proliferation, migration, and early angiogenic responses; they are easy to implement and highly reproducible, but lack physiological relevance. 3D models better recapitulate extracellular matrix architecture and cell-cell interactions, providing higher biological fidelity at the cost of increased technical complexity and expense. Microfluidic systems reproduce hemodynamic forces and microenvironmental gradients with the highest degree of physiological relevance, but are time- and resource-intensive. Models based on induced pluripotent stem cells enable patient-specific investigations and disease modeling, although they can be limited by variability and potential instability. No single in vitro platform fully reproduces the complexity of angiogenesis. Model selection should be aligned with specific research objectives. Integrating 3D culture systems, microfluidics, and artificial intelligence-assisted analysis is particularly promising for advancing angiogenesis research in cardiovascular medicine.

Keywords: Angiogenesis; In vitro models; Cell technologies; Cell cultures; Endothelial cells

Core Tip: Experimental angiogenesis research is rapidly evolving in cardiovascular medicine. In vitro models offer precise control and stable experimental conditions with favorable cost-effectiveness compared with ex vivo and in vivo approaches. Limitations include incomplete reproduction of physiological conditions, particularly in 2D systems. Wider implementation of 3D culture, microfluidic platforms, and artificial intelligence should be considered to achieve more comprehensive and physiologically relevant studies of angiogenesis despite greater complexity and cost.