Table of Contents

November 2002; 2 (7)

Speaking of Pharmacology



  • On average, the human heart beats 100,000 times a day and it is in a person’s best interest to have the heart move blood as efficiently as possible. For example, imagine a wet rag: squeezing the rag in your fist does not remove as much water as wringing the same rag between two hands. Thus, in hearts as in rags, torsional wringing, as opposed to squeezing, more thoroughly empties the heart of blood. Recent reports indicate that the activity and the distribution of myosin light chain kinase (MLCK) in the myocardium is key to this process. MLCK-dependent phosphorylation of the regulatory light chain (R-LC), a subunit of the myosin molecule, may lead to increased force and power of contraction. It is the asymmetric distribution of MLCK in the myocardium that allows for torsional wringing rather than squeezing. Specifically targeting MLCK expression in the heart might, in the future, lead to promising therapies that counteract cardiomyopathy.

  • During the process of heart failure, the myocardium undergoes progressive remodeling. Local proinflammatory cytokines, such as tumor necrosis factor-α, exacerbate the process by promoting chronic inflammation in the heart. Recent evidence indicates that angiotensin II (AII) may participate upstream of and in concert with proinflammatory cytokines to enhance the expression of these cytokines, thus augmenting the remodeling process. Other growth factors, such as leptin, ameliorate the effects of AII and proinflammatory cytokines. Holycross and Radin discuss the antagonistic roles of cytokines in heart failure.

  • Autoimmunity, first described as "horror autotoxicus" (fear of self-poisoning) by Paul Ehrlich in 1900, refers to the inability of one’s own immune system to recognize and discriminate its "self" from non-self or that which is foreign to the body. Defects in immune sureveillance leading to autoimmunity can result in occlusion of the vasculature, organ failure, and death. To better treat the specific disease states that arise from chronic autoimmunity, a greater understanding of the genetic factors that underlie much of autoimmunity (or the predisposition to it) must be garnered. A recent report demonstrates that mutations in both Fas (whose product directs the apoptosis of cells) and the Sle (systemic lupus erythematosus) locus in mice result in enhanced autoimmunity. Cohen provides a brief overview on autoimmunity with regard to SLE, and discusses what is known about the function of the genes in the Sle locus and how better therapies might arise from understanding how Sle and Fas proteins interact.



  • As the heart ages, it undergoes certain adaptations, some beneficial and compensatory and some not, in response to changes in arterial plasticity. Simple interventions including exercise and dietary changes, such as the ingestion of specific polyunsaturated fatty acids, may provide lasting cardiovascular benefits. Better understanding of the physiological changes that occur in the aging heart, from the molecular to the whole organ, may lead to more effective future treatments and preventive medicine.

  • Smooth muscle has long been recognized for its role in controlling the contractility of hollow organs, including the vasculature, gastrointestinal tract, airways, and uterus. The dynamic functions of smooth muscle cells in the genesis and remodeling of these organs and organ systems, have, however, gone largely unappreciated. Particularly during inflammation, smooth muscle cells synthesize a variety of signaling proteins that can contribute to both disease and its amelioration.

Net Results

Beyond the Bench