oa Cadmium Modulates Expression Of Vascular Alpha Adrenoceptors And Aortic Smooth Muscle Cells Phenotype

Cardiovascular diseases (CVDs) remain the leading cause of death worldwide, including Qatar. Hypertension is one of the most common CVDs that contribute to this mortality. Cadmium is a well-known pollutant that has been suggested to be a risk factor for hypertension. However, the underlying mechanisms are still lacking. Very little is known about the effect of cadmium on the expression of vascular alpha- 1 adrenoceptors in vascular smooth muscle cells (VSMCs). This study was therefore undertaken to determine the effect of cadmium on the expression of vascular alpha-1 adrenergic receptors in vitro. Along with that, there are several phenotypic changes could modulate the VSMCs function and contribute to CVDs including hypertension. These changes include hypertrophy, migration and senescence. The second objective of this study was to determine the effect of cadmium on VSMCs phenotype. Human aortic smooth muscle cells (HASMCs) were incubated with different concentrations of cadmium chloride for varying durations. The results indicated that cadmium (Cd) increases the expression of alpha -1 AR in HASMCs in a concentration and time dependent manner. To determine if cadmium modulates the transcriptional activity of alpha -1 AR, cells were pre-incubated with actinomycin D, a DNA-dependent RNA synthesis inhibitor. Interestingly, the cadmium-induced alpha1 AR protein expression was abolished by actinomycin D. Moreover, this expression of alpha- 1 AR was diminished when cells were pre-incubated with H89, a protein kinase A (PKA) inhibitor. This indicates that PKA plays an important role in mediating the Cd-induced expression of alpha- 1 AR. To determine the effect of Cd on VSMCs phenotype, HASMCs were incubated with CdCl2. Our results show that cadmium induces hypertrophy, migration and senescence. Taken together, our results dissect a novel pathway employed by cadmium to increase expression of vascular alpha 1 ARs, a major player in hypertension and VSMCs phenotypic modulation. This new paradigm offers a better understanding and thus potential amelioration of pollution- related CVDs.