Emerging issues in the cellular biology of the cardiovascular system

Current theory suggests that life began in a prebiologic era, progressed to a ribonucleic-deoxyribonucleic cellular era, and finally entered an era characterized by multicellular organisms. If this progression is correct, it is not surprising that, as medicine studies living organisms with increasing sophistication, factors that are initially discovered to have systemic effects are, in many instances, later determined to have paracrine, autocrine or even intracellular ("intracrine") effects. This schema is potentially of value in analyzing the pathogenesis of cardiovascular disease and, in particular, the development of the sequelae of hypertension. A case is made for the idea that the actions of common peptide and nonpeptide factors at local tissue levels can play an important role in the development of atherosclerosis and left ventricular hypertrophy. In making this case, the potential roles of insulin, angiotensin II and other vasoactive factors are considered. In addition, it is argued that some peptide and nonpeptide factors with cardiovascular impact may operate in the intracellular environment, thus broadening prospects for study and intervention. Finally, genomic alterations either spontaneously occurring or resulting from chronic stimulation or viral infection are considered and their potential role is discussed.