Based on the influence of estrogen deficiency, inflammatory markers related to heart remodeling were determined and corresponding telomere lengths compared with those in the chemically induced ovarian failure model (4-vinylcyclohexene diepoxide (VCD)) in female rats. Estrogen deficiency induces cardiovascular dysfunction by increased inflammation, oxidative stress and cellular senescence. Adult female albino rats were used in both groups: (a) controls (untreated) and VCD-treated (undergoing ovarian failure). Blood and cardiac tissue were obtained 6–8 weeks after 15 days of VCD (80 mg/kg) intraperitoneal administration to induce ovarian failure for biochemical, molecular and histopathological analyses. Serum levels of interleukin-6 (IL-6) and C-reactive protein (CRP), as well as telomere length, using quantitative real-time PCR. Moreover, oxidative stress markers were assessed and the expression of estrogen receptor genes were investigated. The results demonstrated a high and significant decrease in serum estrogen levels (indicating ovarian failure) in the sera of the VCD-treated group, which was confirmed by increased serum levels of IL-6 and CRP only. The length of telomeres was significantly reduced in cardiac tissues, which prompted to an enhanced cellular senescence. In addition, levels of oxidative stress were achieved higher due to elevated malondialdehyde (MDA) levels followed by reduced glutathione and nitric oxide. Histopathological examination showed signs of degeneration, inflammatory infiltration and fibrosis in the myocardium. In conclusion, estrogen deficiency-related cardiac remodeling involves a complex web of pathways (such as inflammation, oxidative stress, and telomere shortening) that can be integrated into molecular targets indicating their feasibility to serve as potential predictive biomarkers for cardiovascular disease.