Abstract Introduction Coronary artery atherosclerotic disease is the most common cardiovascular disease and bypass grafting surgery (CABG) is an effective treatment. However, the pathogenic mechanism of coronary arteries atherosclerosis and disease progression is not yet clear. Purpose The use of FT-IR spectroscopy, hyperspectral microscope and mathematical simulation models are some of the tools to predict the morphological and elasticity disorders in the vessel wall due to molecular structure changes. Methods Biopsies of atherosclerotic native coronary arteries from 54 patients (44–85 years), who underwent coronary endarterectomy during bypass grafting surgery (CABG), were examined ex vivo. The FT-IR-spectra were recorded with a Nicolet-6700 spectrometer. Morphological changes of atheromatic plaques were performed with SEM-EDX, Fei-Co. CytoVita-Olympus hyperspectral microscope was used to obtain the cells. Results FT-IR spectroscopy (Figure 1A) showed that the disease affects the protein folding, leading to amyloid formation (beta-sheets), lipid peroxidation and AGEs (Advanced Glycation end products) production. The detection of amorphous CaCO3 (1415 and 872 cm–1) deposits in high lipophilic regions was of high importance. Increased mineral concentration leads to increased formation of crystalline deposits, consisting of CaCO3, CaHPO4, Ca3(PO4)2 and inorganic hydroxyapatite, resulting in arterial stenosis. Hyperspectral images confirmed the formation of micelles (1) due to amyloidosis and calcified cells (2), in agreement with FT-IR, ImageJ analysis data. Mathematical simulation model based on finite element method (Figure 1E) showed that arterial wall damage and elasticity changes were not homogenous. This model provides the time of crystallization of the calcium salts, which play crucial role to stenosis. Conclusions FT-IR spectra showed that the formation of amorphous CaCO3 in the presence of Mg2+, in reach of oxidized lipids regions, inhibit the development of coronary artery stenosis. Excessive of Ca2+ efflux promotes the crystallinity of CaCO3 and Ca3(PO4)2 deposits, leading to the development of atherosclerotic plaques and coronary artery stenosis. Mathematical models approach in a much better way the progression of arterial atherosclerosis. Funding Acknowledgement Type of funding sources: None. Figure 1