Faculty Collaboration Database

Cadmium exposure induces a sex-dependent decline in left ventricular cardiac function. Life Sci 2023 Jul 01;324:121712

Date

04/27/2023

Pubmed ID

37100378

Pubmed Central ID

PMC10246466

DOI

10.1016/j.lfs.2023.121712

Scopus ID

2-s2.0-85153605198 (requires institutional sign-in at Scopus site)   4 Citations

Abstract

AIMS: Cadmium exposure is a worldwide problem that has been linked to the development of cardiovascular disease. This study aimed to elucidate mechanistic details of chronic cadmium exposure on the structure and function of the heart.

MAIN METHODS: Male and female mice were exposed to cadmium chloride (CdCl₂) via drinking water for eight weeks. Serial echocardiography and blood pressure measurements were performed. Markers of hypertrophy and fibrosis were assessed, along with molecular targets of Ca²⁺-handling.

KEY FINDINGS: Males exhibited a significant reduction in left ventricular ejection fraction and fractional shortening with CdCl₂ exposure, along with increased ventricular volume at end-systole, and decreased interventricular septal thickness at end-systole. Interestingly, no changes were detected in females. Experiments in isolated cardiomyocytes revealed that CdCl₂-induced contractile dysfunction was also present at the cellular level, showing decreased Ca²⁺ transient and sarcomere shortening amplitude with CdCl₂ exposure. Further mechanistic investigation uncovered a decrease in sarco/endoplasmic reticulum Ca²⁺-ATPase 2a (SERCA2a) protein expression and phosphorylated phospholamban levels in male hearts with CdCl₂ exposure.

SIGNIFICANCE: The findings of our novel study provide important insight into how cadmium exposure may act as a sex-specific driver of cardiovascular disease, and further underscore the importance of reducing human exposure to cadmium.

Author List

Fitch ML, Kabir R, Ebenebe OV, Taube N, Garbus H, Sinha P, Wang N, Mishra S, Lin BL, Muller GK, Kohr MJ

Author

Brian L. Lin PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cadmium
Calcium
Cardiovascular Diseases
Female
Humans
Male
Mice
Myocytes, Cardiac
Sarcoplasmic Reticulum Calcium-Transporting ATPases
Stroke Volume
Ventricular Function, Left