Mechanistically, SMC dysfunction (i.e., hypercontractility) has been found to precede endothelial dysfunction in obesity [22] suggesting a potential role for SMC-MR signaling to contribute to impaired coronary and cardiac function in obese females via crosstalk between SMC and other cells in the heart. The gene discussed is NR3C2; the disease is obesity due to melanocortin 4 receptor deficiency.