The lox blood pressure series#

Circadian regulation of BP is an especially important topic. This mechanism likely underlies the established daily variations in most physiological functions, including sleep/wake patterns, respiration, metabolism, body temperature, and blood pressure (BP). We now know that the circadian clock components function in every cell type and tissue. For example, the clock mechanism has been linked to regulation of ion transport genes in the kidney and metabolic pathway genes in the liver. In a given tissue, 10-15% of genes are likely to be regulated by this molecular circadian clock, and the target genes of the clock vary in a tissue-specific manner. Indeed, nearly 50% of all expressed genes throughout the entire body are subject to this mechanism of circadian regulation. Michael Young on the molecular mechanisms of the clock, including new insights revealed by structural biology analysis of clock proteins, see. For an excellent and detailed review by recent Nobel Prize winner Dr. This transcriptional mechanism is regulated post-translationally through the action of key circadian kinases such as CK1Оґ/Оµ, and protein turnover is affected by FBXL family members leading to proteasome-mediated degradation. ROR and REV-ERB feedback on and mediate opposing action on BMAL1 gene expression. In the negative feedback loops, PER and CRY antagonize BMAL1/CLOCK action. In mammals, BMAL1 and CLOCK comprise the positive loop of the circadian mechanism in which they drive expression of the Period and Cryptochrome genes (encoding PER1-3, CRY1 and 2), and the Ror and Nr1d1/2 genes that encode the nuclear receptors ROR and REV-ERB (RORО±-Оі, REV-ERBО± and ОІ).

The lox blood pressure series#

These transcription factors function in a series of feedback loops that drive circadian gene expression for the core clock genes and an extensive number of target genes. The core molecular components of the circadian clock are a group of transcription factors that regulate gene expression. Understanding how these molecular clocks regulate the circadian rhythm of BP is critical in the treatment of circadian BP dysregulation and hypertension.

Additional tissue-specific studies of the molecular clock mechanism are needed, as well as clinical studies including more diverse populations (different races, female patients, etc.), which will be critical to fully understand the mechanism of circadian regulation of BP. In this review, we highlight research of human and mouse circadian models that has provided insight into the roles of these molecular clocks and their effects on physiological functions. The mechanism of this dysregulation is unknown and is a growing area of research. The dysregulation of this circadian pattern of BP, with or without hypertension, is associated with increased risk for cardiovascular disease. The kidney, brain, nervous system, vasculature, and heart have been identified through the use of mouse models and clinical trials as peripheral clock regulators of BP. Light and food cues entrain these clocks to the time of day and this synchronicity contributes to the regulation of a variety of physiological processes with effects on overall health. These circadian rhythms are controlled by the central clock in the suprachiasmatic nucleus (SCN) of the hypothalamus and peripheral clocks located throughout the body. Circadian rhythms in body temperature, sleep-wake cycles, metabolism, and blood pressure (BP) are just a few examples. Most bodily functions vary over the course of a 24 hour day.