Increasing evidence reveals that low-density lipoproteins (LDL) and gender are significant risk factors in the development of cardiovascular disease (CVD). The long-term objective of this investigation is to determine the possible relationship between sex hormones, LDL, and the development of CVD. The specific aims of this investigation include: (1) to evaluate the effect of estrogen (E) and testosterone (T) on the proliferation of MRC-5 cells, (2) to investigate the role of E and T on the viability of MRC-5 cells exposed to physiological and supraphysiological levels of LDL, and (3) to evaluate the morphological changes associated with E, T, and LDL, alone or in combination, on MRC-5 cells. Proliferation rates, biochemical marker analysis, and morphological evaluations were performed following standard laboratory procedures. The results of the investigation revealed that physiological and supraphysiological levels of LDL, alone, or in combination with E and T, induced significant changes in the functional and structural capacities of MRC-5 fibroblasts throughout the experimental phases (24, 48, and 72 hours) in comparison to the control groups. MRC-5 cells exposed to T and LDL resulted in increased proliferation rates and remarkable cellular damage. In contrast, E exposure induced decreased levels of MDA compared to T exposure. Results from this investigation suggest the development of collagen matrix post cardiovascular necrosis can be attributed to the presence of T. This response could be triggered directly at the fibroblast level or by altering the physiochemical characteristics of LDL.