Effects of Thyroid Hormone Metabolite Treatment for Postmenopausal Heart Repair
Abstract
Critical Problem: Cardiovascular disease continues to be the leading cause of death for women in the United States, and women are diagnosed with heart failure later in life compared to men. Further, female patients with heart failure have the highest annual percentage increase in hospitalization rates. Since sex differences exist in heart disease in men and women, including the presentation of symptoms, average age of clinical manifestations, and mortality and prognosis after an acute cardiovascular event, sex-specific research for novel treatments and studies dealing with impacts of the endocrine system and menopause on cardiovascular health of women are essential. During menopause there is a decline in circulating sex hormones as well as thyroid function. The reduction of estrogen is correlated with reduced protection from cardiovascular diseases. Studies in premenopausal women show that hysterectomy, which reduces estrogen levels, is associated with higher risk of cardiovascular disease. Similarly, a loss of thyroid hormone is also associated with reduced cardiac health in women. The cardiovascular system is one of the most important targets on which thyroid hormones act. Menopause also alters thyroid function. In fact, women are more prone to thyroid disorders than men. Further, observational studies have found an association between mild hypothyroidism, when an underperforming thyroid gland makes insufficient thyroid hormone, and increased death risk in heart failure patients. Triiodothyronine, also known as T3, is a thyroid hormone. Low T3 syndrome, characterized by low T3 circulating levels, makes heart failure worse. While data supports benefits gained from treating hypothyroid and low T3 heart failure patients with thyroid hormones, this link between low thyroid hormone levels and poor prognosis in cardiac patients is not clearly understood. Adding in multiple factors such as gender, and the presence or absence of sex hormones, such as estrogen, only further complicates this relationship. Innovation: Most cardiology research is concerned with restoration of blood flow to blocked arteries, but this does not address the prevention of future cardiac issues or improve treatments for post-heart attack heart failure. Our study is highly innovative as the loss of estrogen and thyroid hormone are associated with poor cardiac health in women. Our innovation utilizes the effects of thyroid replacement therapy through use of the lesser known, endogenous thyroid hormone metabolite 3,3’-diiodothyronine (3,3 -T2). Formed from the breakdown of triiodothyronine (T3), 3,3 -T2 has been overlooked. The work will also improve our understanding of why thyroid imbalance increases the risk for heart failure while helping reduce hypothyroidism as a risk factor for heart failure through therapeutic administration of 3,3 -T2. Previously, T3 replacement therapy revealed beneficial effects in patients with heart failure and those recovering from cardiac surgery. T3 activates both thyroid hormone receptors alpha and beta to a similar degree, whereas we have found 3,3 -T2 has greater specificity for thyroid hormone receptor alpha. Our research presents a novel therapeutic means to activate thyroid hormone receptor alpha, which is predominantly expressed in the heart, and stimulate signaling pathways that promote heart repair. Therefore, repairing a hypothyroid cardiac state in failing hearts by increasing thyroid hormone alpha receptor levels with 3,3 -T2 will offer a better means to improve cardiac function without detrimental effects. Our study will also significantly add credence that future interventions must consider sex as a potential reason why a condition exists as well as how best to tailor therapeutics to resolve such adverse conditions. Therapy plans that could not only serve as a repair mechanism but also a preventative treatment would create an enormous positive impact on female patients who will all undergo menopause at some poi
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210007
Entities
People
- Carly S Filgueira
Organizations
- Houston Methodist Research Institute
- United States Army